Effect of diet and animal care/housing protocols on body weight, survival, tumor incidences, and nephropathy severity of F344 rats in chronic studies

Diet is an important environmental factor affecting body weight, survival, and age-related diseases of rodents. The NIH-07 open formula diet was the diet used in the National Toxicology Program's (NTPs) rodent carcinogenicity studies from 1980 to 1994. In 1994 the NTP began using a new diet designated the NTP-2000 diet. This paper compares body weight, survival, tumor incidence, and nephropathy severity in untreated control groups of Fischer 344 (F344) rats fed the NTP-2000 or NIH-07 diets, using data from 22 separate 2-year feed and inhalation studies. The feed studies were conducted in 3 different facilities, and all the inhalation studies were conducted in a single facility. During feed studies, rats were group housed in polycarbonate cages and fed diets in powder (mash) form, while in inhalation studies, rats were housed individually in wire mesh cages, and fed diets in pelleted form. Survival was significantly (p<0.05) higher in groups fed NTP-2000 diet compared to the corresponding groups fed NIH-07 diet, irrespective of sex or housing conditions. Use of the NTP-2000 diet was also associated with a decreased incidence of pituitary gland tumors in both sexes and decreased incidences of adrenal pheochromocytoma and preputial gland tumors in males. The incidence and severity of nephropathy was also decreased in animals receiving the NTP-2000 diet, especially males. The decreased nephropathy severity and the decreased incidence of pituitary gland tumors are likely the major factors contributing to the improved survival of rats receiving the NTP-2000 diet relative to those given the NIH-07 diet. These data also support earlier findings that decreased incidences of adrenal pheochromocytoma are associated with reduced nephropathy severity in male F344 rats. Throughout the two-year study female rats receiving the NTP-2000 diet were significantly (p<0.05) lighter than those receiving the NIH-07 diet. However, it is uncertain if this difference can be attributed to the NTP-2000 diet, since implementation of this diet by the NTP approximately coincided with changes in the F344 rat production colony that resulted in somewhat lighter animals being provided to the NTP. Controls from inhalation studies and feed studies differed significantly (p<0.01) in the incidence of a variety of tumors, irrespective of diet. This suggests that differences in animal care and housing protocols may impact tumor incidence in F344 rats, most notably pituitary gland and testis tumors.     

Mortality, major cause of moribundity, and spontaneous tumors in CD-1 mice

Mortality, major causes of moribundity, and spontaneous tumors in CD-1 mice were studied in 891 males and 890 females, which were used as controls in 11 different 2-year chronic and oncogenicity studies during the past 5 years. Average mortality of males and females at 83 weeks of age was 32.6% and 28.6%, respectively, and at 109 weeks of age was 66.4% and 63.3%, respectively. Mortality was significantly lowered in males and females born after 1980 in accordance with an abruptly decreased occurrence of systemic amyloidosis in these animals. The major cause of death or moribundity included systemic arteritis, systemic amyloidosis, auricular thrombosis, glomerulosclerosis, lymphoma, and pulmonary adenocarcinoma in both sexes. Dysuria and hepatocellular carcinoma in males and mammary adenocarcinoma in females were also critical lesions. The major tumors occurring at more than 3% incidence were systemic lymphoma, adenoma/adenocarcinoma of the lung, adenoma/carcinoma of the liver and adenoma/adenocarcinoma of the Harderian gland for males, and systemic lymphoma, adenoma/adenocarcinoma of the lung, adenoma/carcinoma of the liver, leiomyoma/leiomyosarcoma of the uterus, adenoma/adenocarcinoma of the pituitary (anterior), adenoma/adenocarcinoma of the mammary gland and adenoma/adenocarcinoma of the Harderian gland for females. Intralaboratory heterogeneities in the incidence were recorded as follows: systemic lymphoma in 1 of 11 control groups (1/11) and adenoma/adenocarcinoma in 1/11 for males, and systemic lymphoma in 3/11, adenoma/adenocarcinoma of the lung in 2/11, adenoma/adenocarcinoma of the liver in 1/11, and adenoma/adenocarcinoma in 1/11 for females.     

Frequency of spontaneous tumors in Wistar rats in 30-months studies.

Tumors occurring in 450 male and 450 female control rats of the strain Wistar (BOR:WISW (SPF Cpb), breeder: Winkelmann, Borchen) employed in 9 control groups from 7 different 30-month studies were compiled on the basis of histopathology reports. 445 male and 448 female rats were evaluated. The remaining animals were unavailable due to autolysis. A total of 1211 tumors (565 in males, 646 in females) were seen in 716 rats (333 males, 383 females), 251 of which were classified as malignant (100 in males, 151 in females). About 44% of all primary tumors were located in the pituitary and adrenals alone. Average frequencies of primary tumors: pituitary 35.4%, uterus 34.0%, adrenals 26.5%, testes 15.8%, thyroid gland 11.8%, mammary glands 11.4% and 22.5% in females respectively, skin/subcutis 6.3%, ovaries 2.9%, endocrine pancreas 2.5%, hemolymphoreticular system 2.3%, liver 1.9%, heart 1.7% and various other organs showing tumor frequencies of less than 1.5%. Male animals exhibited strikingly more tumors of the adrenals, skin, endocrine pancreas, heart and brain, while pituitary tumors were predominant in females. A comparison of these data with those from 24-month studies in Wistar rats from the same breeder shows a considerable increase above all in the number of primary tumors, the number of tumor bearers as well as the number of tumors in the pituitary, adrenals, testes, mammary glands and heart. An extension of carcinogenicity studies to 30 months probably makes it harder to recognise tumorigenic effects of test substances, at least in some organs, than in two-year studies because of the high and variable spontaneous tumor rates.     

Exercise and the development and persistence of dietary obesity in male and female rats

Adult male and female hooded rats were housed in sedentary conditions or were given free access to a running wheel. Exercising and sedentary rats received either a palatable, mixed, high energy diet with chow (experimental group) or only chow (control group). Exercise reduced the weight gain of the males but not of the females. All experimental groups preferentially selected the palatable foods. Both exercising and sedentary females and the sedentary males became obese compared to their controls, but the exercising males did not. The mixed diet was withdrawn after 10 weeks: thereafter the male and female sedentary experimental groups maintained the elevated body weight. The exercising experimental females showed significant weight loss. Analysis of x-ray photographs indicated that elevated body weight in the experimental rats probably reflected increased deposition of fat and not skeletal growth. The results show that the effect of exercise on the development of dietary obesity is different in males and females, and that sedentary male and female rats can both show persistent dietary obesity after withdrawal of the palatable foods.     

A two-generation chronic mixture toxicity study of Clophen A60 and diethyl phthalate on histology of adrenal cortex and thyroid of rats

This study was undertaken to observe the type of interaction that exists between polychlorinated biphenyls (Clophen A60) and diethyl phthalate (DEP) on the adrenal and thyroid glands of male and female Wistar rats. Animals were divided into four groups of six animals each, group I male and female rats were fed on a normal diet and water ad libitum. Groups II, III and IV male and female rats were given Clophen A60, DEP, or mixture of Clophen A60 and DEP, respectively, each dissolved in corn oil mixed with the diet at 50mg/kg of the diet/day. One hundred days after treatment, females were mated with males for 10 days. Exposure to the pollutants was continued throughout mating, gestation (21 days) until termination at weaning (21 days), which was 150 days of total treatment period of the parental generation. When the F1-generation pups (six males and six females of each group) were 75-100g in weight, they were treated in a similar manner to the parental generation, again for a period of 150 days, with the dose reduced to 25mg/kg of the diet/day in all treated groups. After 150 days of treatment, animals were sacrificed and histology of the adrenal and thyroid glands was asessed. An antagonistic interactive effect of treatment was seen in male parental and F1-generation rats, while an inhibitory type of interactive effect was observed in female rats. In the zona fasciculata region of the adrenal cortex of treated rats of both generations, vacuolations and degeneration were seen in samples from male animals and intracellular vacuolations in samples from females. A synergistic interactive toxic effect to the thyroid gland was observed in treated parental generation male rats, and mild changes in F1-generation-treated male rats, showing follicular shrinkage, loss of thyroglobulin and fibrosis of the interfollicular epithelium. In females, an antagonistic effect to the thyroid gland was observed in both parental and F1-generation-treated rats, showing similar effects as observed in males. From this study, we can conclude that combined administration of Clophen A60 and DEP shows an enhanced toxic effect on adrenal glands of F1-generation male and female rats, but the effect is much more marked in the thyroid gland of F1-generation male rats, and seen to a lesser extent in F1-generation female rats.     

Spontaneous tumors of 2000 Wistar TNO/W.70 rats in two-year carcinogenicity studies

Eleven two-year toxicity/carcinogenicity experiments in control Wistar TNO/W.70 rats were started between 1973 and 1976. Tumors occurring were compiled on the basis of histopathological reports. Of the 1,000 male and 1,000 female rats at the beginning of the studies, 962 males and 968 females were evaluated. The remaining animals were unavailable due to autolysis or early death (before day 400). The histopathologic diagnosis for the eleven reports were performed by five different pathologists or groups of pathologists. A total of 827 tumors (375 in males and 452 in females) was seen in 686 rats (303 males, 383 females). 183 tumors (67 in males, 116 in females) were classified as malignant. 719 (86.9%) of all tumors and 120 (65.6%) of all malignant tumors were located in endocrine organs (pituitary, thyroid, adrenal, pancreatic islets) or in genital organs (testes, epididymides, seminal vesicles, ovaries, uterus, mammary gland). Average incidences of primary tumors found in the following organs were: pituitary 20.0%, thyroid 9.6%, uterus 9.2%, adrenals 4.1%, mamma 3.2%, testes 2.9%, ovaries 1.8%, skin 1.4% and 17 other organs each with a tumor frequency below 1%. This wide spectrum of spontaneous tumors with a mostly low incidence makes the Wistar rat a preferred strain for carcinogenicity studies. Despite nearly identical husbandry conditions, a marked variability was observed among experiments regarding the general incidence of benign and/or malignant tumors, particular tumors, and number of tumor-bearing animals. Differences in mortality among experiments had no pronounced effect on the variability of tumor incidences. Different evaluation criteria used by different pathologists did not appear to be a major cause of the observed variability with the probable exception of lesions in endocrine organs. The major cause would seem to be the biological variability of the animal material. The observed marked variability of tumor incidences between experiments would indicate that a considerable natural variability may also occur between groups of one carcinogenicity study. Therefore, information on historical control tumor data from the same rat strain kept under similar conditions is needed to interpret the incidences of tumors in carcinogenicity experiments.     

Effect of subchronic oral sulfamethazine administration on Fischer 344 rats and B6C3F1 mice

One hundred and forty four Fischer 344 rats and 144 B6C3F1 mice of both sexes were fed either a control diet or a diet containing 300, 600, 1200, 2400 or 3600 ppm sulfamethazine for 90 days. They were then necropsied and tissue specimens were evaluated for pathological changes by light and transmission electron microscopy. No gross or light microscopic lesions related to sulfamethazine administration were evident in the mice. Thyroid gland enlargement was evident at necropsy in one half of the rats (12 of 24) which received the 3600 ppm dosage level of sulfamethazine and in 1 of 24 rats fed the 2400 ppm level. By light microscopy, thyroid gland hyperplasia was evident in rats which received all five dosage levels of the compound, but the change was more pronounced and of a greater incidence in those administered the higher concentrations. This effect was observed in rats of both sexes but its incidence was greater in males than in females among the groups receiving the lower concentrations of compound. Ultrastructural changes included markedly dilated rough endoplasmic reticulium, altered microvilli and diminished colloid droplets involving the thyroid follicular cells and compartmentalization of colloid within the follicular lumina.     

Twenty-four-month oral carcinogenicity study of ebrotidine in rats

Three groups of Sprague-Dawley CD rats (males and females) were initially administered p.o. with ebrotidine, a novel H2-receptor antagonist, mixed with the diet, at 50, 200, and 500 mg/kg/d, respectively. Two concurrent control groups of animals were used. After 13 months, initial 200 mg/kg was lowered to 150 mg/kg, and a new group was administered with 300 mg/kg, due to the body weight reduction observed in the top dose group. After 24 months, survivors were killed and necropsied, and a histopathological study was performed. The frequencies of the different tumour types that were found were not raised due to the treatment. Lower frequencies of some types of pituitary and mammary gland tumours, in the groups treated with the higher doses, were the only statistically significant changes. Among the non-neoplastic effects, a lower body weight increment and food consumption (500 and 300 mg/kg, both sexes), lower survival (500 mg/kg, males), presence of lipoid pneumonia (500 mg/kg, only in males, and 300 mg/kg, both sexes), and lithiasis in urinary system (500 mg/kg) were observed. No changes in gastric mucosa (the main target organ) were attributable to ebrotidine. Regarding the non-neoplastic effects, 150 mg/kg was the no observed adverse effect level. According to the previous results of the carcinogenicity study in mice, conjointly with those of the study in rats reported here, there is no evidence of carcinogenic risk either in males or in females in these species.     

Morphological effects of subchronic oral sulfamethazine administration on Fischer 344 rats and B6C3F1 mice

One hundred and forty-four Fischer 344 rats and 144 B6C3F1 mice (72/sex/species) were fed either a control diet or a diet containing 300, 600, 1200, 2400 or 3600 ppm sulfamethazine for 90 days. They were then necropsied and tissue specimens were evaluated for pathological changes by light and transmission electron microscopy. No gross or light microscopic lesions related to sulfamethazine administration were evident in the mice. Thyroid gland enlargement was evident at necropsy in one half of the rats (12 of 24) which received the 3600 ppm level of sulfamethazine and in 1 of 24 rats fed the 2400 ppm level. By light microscopy, thyroid gland hyperplasia was evident in rats which received all 5 dose levels of the compound, but this change was more pronounced and more frequent in those animals administered the higher concentrations. This thyroid hyperplasia was observed in rats of both sexes, but with greater incidence in males than in females, among the groups receiving the lower concentrations of compound. Ultrastructural changes included markedly dilated rough endoplasmic reticulum, altered microvilli, and diminished colloid droplets involving the thyroid follicular cells and compartmentalization of colloid within the follicular lumina.     

Mammary gland tumors in irradiated and untreated guinea pigs

This is a report of mammary gland tumors from 62 guinea pigs. The tumors arose in the terminal ductal-lobular units as either lobular acinar carcinoma or cystadenocarcinoma or as papillary carcinomas within large ducts near the mammilla. About half the number of the males had terminal ductal-lobular carcinomas and all but 2 of the papillary duct carcinomas also arose in males. Large tumors frequently exhibited squamous, chondromatous, osseous, fatty and myoepitheliomatous types of tissues. In 2 irradiated males and 1 female the tumors metastasized. Whole-body irradiation did not produce significant changes in the number or sex distribution or in the morphology of mammary gland tumors in inbred or outbred guinea pigs. All females had cystic ovaries without increase in granulosa cells, 24 (66.6%) had uterine tumors and 13 (34.2%) had adrenal gland tumors; all males had atrophic testes, 5 (16.5%) had testicular and 6 (22.2%) had adrenal gland tumors.     

Mutations induced by 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) in cecum and proximal and distal colon of lacI transgenic rats

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a food-borne mutagen and carcinogen that induces tumors of the colon and the prostate gland in male rats and of the mammary gland in female rats. In this study we describe the frequency and specificity of PhIP-induced mutations in the cecum, proximal colon and distal colon of male and female lacI transgenic rats. This is the first report of mutational data from discrete regions of the colon. After 61 days of treatment with 200 p.p.m. PhIP mixed into the diet, PhIP-induced mutant frequencies were elevated 7-fold in the cecum and 14- to 21-fold in the colon of male and female rats compared with untreated controls. PhIP-induced mutant frequencies increased significantly (overall trend, P < 10(-4)) along the length of the colon of both males and females, with cecum < proximal colon < distal colon. A total of 754 PhIP mutants (363 male, 391 female) were sequenced to provide the mutational spectra for each of the three tissue sections from males and females. These mutational spectra consisted predominantly of G:C-->T:A and G:C-->C:G transversions and deletions of G:C base pairs. There were no significant differences between the mutational spectra with respect to sex or position in the colon. Therefore, we surmise that following induction of mutations by PhIP in male and female colons, non-mutagenic factors, possibly hormonal, preferentially influence the formation of tumors in the colon of male rats.     

The microscopy of “brown degeneration” in the adrenal gland of the mouse

“Brown degeneration,” a pigmentary process of the adrenal gland of the mouse, was consistently induced by administration of ethinyl estradiol. Mice similarly treated with diethylstilbestrol or peanut oil (control) developed only small amounts of pigment. Histochemically, the pigment was ceroid and had its origin in the inner cells of the cortex in both females and males, with the fully developed pigmentation distributed in the cortex in animals of both sexes, and also in the medulla in males. Ultrastructurally, ceroid formation progressed from small pigment granules morphologically similar to lysosomes, to large composite, pleomorphic pigment bodies composed of unique granular configurations and membranous components. The ceroid deposits were interpreted to represent lipid products resulting from altered fat metabolism.     

Sex and diet affect the behavioral response of rats to chronic mild stressors

To investigate the interaction between sex, stressors, and dietary choice in rats, a preferred diet under the influence of chronic mild stressors was empirically determined to consist of soybeans and cookies in addition to lab chow. This preferred mixed diet was then tested for its influence on several behavioral tests at the end of prolonged exposure to the potential stressors. Rats of both sexes decreased their frequency of rearing but increased their attention to novelty in response to stressors. In the elevated plus maze, diet interacted with exposure to stressors to influence time spent in the open arm in females but not males. In the forced swim test, females but not males fed the mixed diet showed increased immobility, whether exposed to stressors or not. Finally, females but not males showed a differential effect of diet under stressors on the sucrose preference test, but this result was confounded by estrus cycling, demonstrating the importance of this factor in analyzing behavior in females. These results suggest that male and female rats differ in their susceptibility to the behavioral-modifying influences of stressors. And to the extent that diet serves as a coping mechanism, it does so differently in males and females.     

An immunocytochemical study of pituitary adenomas and focal hyperplasia in old Sprague-Dawley and Fischer 344 rats

Spontaneous pituitary tumors occurring in groups of 100 Sprague-Dawley (SD) and 100 Fischer 344 (F344) rats of each sex on a 2-year aging study were characterized by immunocytochemistry. The SD strain had a total of 75 tumors with 10% in males and 65% in females. Tumors immunoreactive for prolactin (PRL) alone were the most common tumor (64%) with the immunonegative tumor being the second most common (17.3%). F344 rats had a total of 62 tumors with 26% in males and 36% in females. The majority of the tumors were reactive for prolactin alone (56.5%) and tumors reactive for both growth hormone (GH) and PRL were the second most common (21%). Most tumors were immunoreactive for only 1 hormone; however, both strains had tumors that expressed multiple hormones in unusual combinations.     

Learning and memory disabilities in young adult rats from mildly zinc deficient dams

Three experiments were conducted to test the behavior of the offspring of rat dams (ZD) fed a mildly zinc deficient diet (10.0 micrograms Zn/g) during pregnancy and lactation. Since zinc deficiency causes anorexia, a second group of rat dams (PF) was fed the same quantity of the diet during gestation and lactation as was consumed by their ZD mates. A third group of rats (AL) was fed the diet ad lib during gestation and lactation. The PF and AL dams were given zinc supplemented (25.0 micrograms Zn/ml) drinking water whereas the ZD dams were given double distilled, deionized drinking water. After weaning, the offspring of all dams were fed Purina Laboratory Chow ad lib until they were 100 days old. The offspring were then reduced to 85% of their ad lib weight and tested on a 17-arm radial maze for memory and learning. In Experiments 1 and 2, the ZD males suffered a significant learning deficit when compared to the AL males. Whereas the PF males suffered a significant learning impairment in Experiment 1, the learning deficit of the PF group was not as severe as the deficit of the ZD group. There was no impairment in reference (long-term) memory for any of the groups. In Experiment 3, significant differences in working (short-term) memory were found among the three groups of females. The ZD group was significantly inferior in working memory when compared to the PF and AL groups. No significant differences in working memory were found between the PF and AL groups.     

Post weaning high fat feeding affects rats' behavior and hypothalamic pituitary adrenal axis at the onset of puberty in a sexually dimorphic manner

Feeding adult rats with high fat (HF) diets can alter their hypothalamic pituitary adrenal (HPA) axis responsiveness. In the present study, we examined the effect of a high fat diet, applied in rats from weaning to puberty, on their behavior and HPA axis status at puberty onset. Wistar rats of both sexes were fed postweaning with two diets containing either 24% fat (high fat, HF) or 4.3% fat (normal chow) by weight. HF enhanced puberty onset in female rats, without increasing body weight gain in either sex, compared with chow-fed animals. In the forced swim test, HF males exhibited a more active behavioral response on the first day, whereas HF females a more passive response during the second day of the test, as compared with their chow-fed counterparts. In the open field test, HF females showed increased sniffing but reduced rearing, compared with chow-fed females and were less explorative than HF males in the central arena. All animals could learn and recall a water maze task though HF males spent more time in the opposite quadrant than chow-fed males during memory test. The HPA axis status of these animals was investigated under basal conditions. Pubertal fat-fed males had lighter adrenals, while females heavier ones, compared with their counterparts. In addition, plasma corticosterone levels of female rats were increased and glucocorticoid receptor levels in their hypothalamus were reduced due to fat diet, while in males no such changes were detected. We conclude that HF feeding during the prepubertal period can affect behavior and the HPA axis of rats at puberty onset, well before the appearance of the obese state, in a sexually dimorphic manner. Fat diet impacted more the female HPA axis, suggesting that their system is more sensitive to fat-induced nutritional imbalance during adolescence. Present data suggest that the fat-induced nutritional imbalance in young females may lead to neuroendocrine dysfunction that in turn may trigger the appearance of stress-related disorders during adolescence.     

A reinvestigation of brindley's gland exocrine compounds of Rhodnius prolixus (Hemiptera: Reduviidae)

A chemical, electrophysiological and behavioral study was carried out to analyze the volatile compounds of the Brindley's gland of Rhodnius prolixus St?l. Six compounds were found in the Brindley's gland of males and females: acetic, isobutyric, caproic acids and three compounds not identified. The mass spectra of the unidentified compounds have the appearance of a propionate ester, a butyrate ester and a valerate ester. There was no difference in the concentration of these compounds in the glands of males and females. The major component was isobutyric acid. The electroantennographic (EAG) evaluation of isobutyric, acetic, and caproic acids elicited weak responses. With both sexes, the EAG responses for the acids were no different from the control response at any of the doses evaluated (1, 10, 100, and 500 microg). The behavioral response of males and females to acetic, isobutyric, and caproic acids at 1, 5, and 10 microg and binary and tertiary mixtures of the three compounds was evaluated in a Y-olfactometer. Males showed preference for acetic acid at a dose of 1 microg, but not at 5 or 10 microg. Females showed preference for this compound at the dose of 5 microg. Males showed preference for isobutyric acid at 1 and 5 microg, but not at 10 microg. Females did not show any preference for isobutyric acid. Males were attracted to caproic acid at the dose of 1 and 10 microg. Females were attracted to the caproic acid. Males, but not females, preferred the mixture of acetic and isobutyric acids over control. Neither males nor females showed preference for the mixture of acetic and caproic acids or hexane control. Females, but not males, were attracted to the mixture of the isobutyric and caproic acids. Only males showed a positive response for the tertiary mixture of the acids.     

Odor modulation of ventral scent gland marking in the Mongolian gerbil

Gerbil odors were allowed to accumulate in individual home cages for several months in order to provide stable olfactory stimuli that might modulate the number of ventral scent gland marks produced by both male and female Mongolian gerbils. Male marking levels for most test conditions were 2-3 times larger than those in females. In general, the relative patterns of responsiveness to particular odors were similar in both sexes. The number of scent marks in home cages was significantly smaller than the number obtained in clean cages. This suppression was not strongly dependent on the odors emanating from an individual's own ventral gland sebum. Marking levels in the home cages of other gerbils were substantially higher than those seen in the test animal's own cage and were maximal in the home cages of other males. Behaviorally receptive females marked at significantly higher levels in home, clean, and conspecific cages than did nonreceptive females. Conspecific urine odors, especially those from females, increased marking levels significantly over those obtained in home cages. In males, home cage marking was significantly enhanced by the presence of a female. Females, on the other hand, marked at similar levels in home cages whether a potential mating partner was present or not. Both sexes showed significant reductions in marking levels in another's cage if the resident animal was present. These results suggest that when sufficient gerbil-related odors are available to a test animal, its rate of scent-marking is altered, depending on the particular odor environment. Some gerbil-related odors increase marking levels, whereas others decrease marking. Scent-marking then, like other olfactory guided behaviors and odor preferences, is context specific.     

Gender differences in the incidence of background and chemically induced primary pulmonary neoplasms in B6C3F1 mice: A retrospective analysis of the National Toxicology Program (NTP) carcinogenicity bioassays

The National Toxicology Program (NTP) database of technical reports on carcinogenicity bioassays has been interrogated for the incidence of primary pulmonary neoplasms in B6C3F₁ mice. A total of 170 study reports were selected, from studies that completed the in-life phase during 1983–2007, which included neoplasm incidence data for 180 control groups comprising both male and female mice. The incidence (median and inter-quartile range) of males with alveolar/bronchiolar adenoma was 16% (12–20%), and for females it was 5% (2–8%); the incidence of males with alveolar/bronchiolar carcinoma was 8% (4–12%), and for females it was 2% (0–4%); and the incidence of males with combined alveolar/bronchiolar adenoma or carcinoma was 24% (18–30%), and for females it was 8% (6–12%). Comparing the incidence of animals bearing these lesions on a per study basis showed the median incidence in males to be 3.0-fold, 2.0-fold, and 2.8-fold higher than in females. The incidence of other primary pulmonary neoplasms was <10% of the alveolar/bronchiolar neoplasms. Comparison of gender-specific response to lung tumorigens showed that the increase in incidence of tumors above control levels was greater in females than in males.     

湖南农村土家族成人的体型特征

目的 探讨湖南农村土家族成人的体型特征。 方法 采用Heath-Carter人体测量体型方法,对976名（男性528人,女性448人）湖南农村土家族成人的体型进行评价。 结果 土家族平均体型男性为偏内胚层的中胚层体型(3.43-5.35-1.61),女性为内胚层 中胚层均衡体型(5.18-5.38-1.01);随着年龄增长,男女性的内因子值和中因子值均先增加后下降,而外因子值先下降后递增;各年龄组男性内因子值均明显低于女性,中因子值男女性差异无显著性,多个年龄组男性的外因子值明显高于女性。 结论 湖南农村土家族成人骨骼、肌肉系统较发达,男性体型较为修长,女性皮下脂肪较发达,体态丰满。30个乡村族群中,土家族成人的中因子值较大,外因子值和内因子值较小,体型与木雅人、尔苏人等接近。