Beef tallow, but not perilla or corn oil, promotion of rat prostate and intestinal carcinogenesis by 3,2'-dimethyl-4-aminobiphenyl.

The modifying effects of three kinds of fat (corn oil, beef tallow or perilla oil, each at 20% in the diet) on F344 rat prostate carcinogenesis induced by 3,2'-dimethyl-4-aminobiphenyl (DMAB) were investigated. Non-invasive carcinomas of the ventral prostate were induced by DMAB alone and invasive carcinomas of the other prostate lobes and seminal vesicles by DMAB and testosterone propionate (TP). Eight groups of F344 rats were initiated with 50 mg / kg body weight of DMAB at 2-week intervals for the first 20 weeks, four also receiving TP, extended until week 60. The animals received basal chow powder diet or one of three high fat diets throughout the experiment (60 weeks). One further group served as a non-carcinogen-treated control maintained on basal chow powder diet. Beef tallow significantly increased the development of ventral prostate carcinomas with DMAB alone (from 15 to 45%, P < 0.05), while perilla oil reduced the incidence of prostatic intraepithelial neoplasia (PIN) in the ventral lobe of rats given DMA + TP (from 70 to 10%, P < 0.01), but not in those given DMAB alone. No other effects of high fats were observed regarding PIN or invasive cancers of the dorsolateral and anterior prostate or seminal vesicles. A satellite experiment demonstrated that all high fat diets for 4 weeks increased the 5-bromo-2-deoxyuridine (BrdU) labeling index of prostate epithelial cells, suggesting that a high fat intake, irrespective of the fatty acid composition, may accelerate cell kinetics in the prostate. Of the three high fat diets, beef tallow was also found to increase intestinal carcinogenesis. Thus, the present data revealed carcinogenesis in the prostate and intestine to be promoted by beef tallow.     

Decrease of Prostaglandin E2 and 5–Bromo–2'–deoxyuridine Labeling but Not Prostate Tumor Development by Indomethacin Treatment of Rats Given 3,2'–Dimethyl-4-aminobiphenyl and Testosterone Propionate

The modifying effects of indomethacin (IM) on rat prostate carcinogenesis induced by 3,2'–dimethyl–4–aminobiphenyl (DMAB) were investigated. F344 rats were given 50 mg/kg body weight of DMAB at 2–week intervals for 20 weeks and then received IM at a dose of 20 ppm in the drinking water for 37 weeks. Separate groups additionally received testosterone propionate (TP) in Silastic tubes throughout the experiment. DMAB alone induced carcinomas in situ in the ventral lobe and in combination with TP caused invasive carcinomas of the dorso–lateral and anterior lobes and seminal vesicles. No clear suppression by IM of development of in situ carcinomas or in vasive carcinomas was observed. In a short–term satellite experiment, it was revealed that prostaglandin E₂ (PGE₂) levels in the dorso–lateral prostate and seminal vesicles, but not the ventral prostate, were significantly reduced by IM and that TP itself also suppressed PGE₂ levels. The 5–bromo–2'–deoxyuridine labeling index in the ventral prostate was significantly decreased by IM administration. These results indicate that while IM can efficiently suppress tissue PGE₂ levels, it does not inhibit tumor development in the prostate or seminal vesicles of rats in the present model.     

Suppressive effects of dietary genistin and daidzin on rat prostate carcinogenesis.

High intake of phytoestrogens through soybeans and their products is thought to be associated with low incidences of prostate and / or breast cancer in Asian countries. Possible chemopreventive effects of genistin or daidzin on rat prostate carcinogenesis were therefore investigated. Male F344 rats were given 10 biweekly subcutaneous injections of 3,2'-dimethyl-4-aminobiphenyl (DMAB) and then either genistin or daidzin in the diet at a concentration of 0.1% for 40 weeks. Other groups of rats given DMAB were treated with genistin or daidzin together with a high dose of testosterone propionate (TP). Both genistin and daidzin reduced the numbers of ventral prostate carcinomas (P < 0.05), with a tendency for decrease in incidence. Invasive carcinomas which developed in the anterior prostate and seminal vesicles with TP were, however, not influenced by the two isoflavones. Thus, the present data suggest that genistin and daidzin possess anti-cancer effects at relatively early stages of prostate cancer development, providing experimental support for epidemiological findings.     

Suppressive Effects of Dietary Genistin and Daidzin on Rat Prostate Carcinogenesis

High intake of phytoestrogens through soybeans and their products is thought to be associated with low incidences of prostate and/or breast cancer in Asian countries. Possible chemopreventive effects of genistin or daidzin on rat prostate carcinogenesis were therefore investigated. Male F344 rats were given 10 biweekly subcutaneous injections of 3,2'-dimethyl-4-aminobiphenyl (DMAB) and then either genistin or daidzin in the diet at a concentration of 0.1% for 40 weeks. Other groups of rats given DMAB were treated with genistin or daidzin together with a high dose of testosterone propionate (TP). Both genistin and daidzin reduced the numbers of ventral prostate carcinomas (P<0.05), with a tendency for decrease in incidence. Invasive carcinomas which developed in the anterior prostate and seminal vesicles with TP were, however, not influenced by the two isoflavones. Thus, the present data suggest that genistin and daidzin possess anti-cancer effects at relatively early stages of prostate cancer development, providing experimental support for epide-miological findings.     

Lobe specific effects of testosterone and estrogen on 3,2'-dimethyl-4-aminobiphenyl-induced rat prostate carcinogenesis

We have previously shown that chronic administration of a pharmacological dose of testosterone propionate (TP) after treatment with the carcinogen, 3,2'-dimethyl-4-aminobiphenyl (DMAB), results in development of invasive and metastatic adenocarcinomas arising from the dorso-lateral and anterior prostate, as well as the seminal vesicles. Co-administration of ethinyl estradiol (EE) with TP increased the yield of carcinomas in the lateral and anterior lobes. In the present experiment, male F344 rats were treated with DMAB for 20 weeks and then co-administered a pharmacological dose of TP together with various doses of EE for 40 weeks. Without hormone(s) administration, carcinomas were confined to the ventral prostate and all were of intra-acinar type. TP administration suppressed development of the ventral prostate carcinomas but caused invasive carcinomas of the lateral and anterior lobes and of seminal vesicles and intra-acinar carcinomas in the dorsal prostate. The appearance of carcinomas in the lateral and anterior prostate was increased by co-administration of EE in a dose-related fashion but carcinomas of the seminal vesicles were inversely reduced. The suppressive influence of TP on ventral carcinoma development was overcome by only the highest dose of EE. It is concluded that estrogen can modify the enhancing effects of TP on induction of rat prostate and seminal vesicle carcinomas in a dose-related fashion with lobe specificity.     

Comparison of the effects of dietary beef tallow and corn oil on pancreatic carcinogenesis in the hamster model

We previously reported an enhancement of pancreatic carcinogenesis induced by N-nitrosobis(2-oxopropyl)amine (BOP) in hamsters fed diets containing high levels of corn oil. The research presented here compared diets high in corn oil with those high in beef tallow in the enhancement of pancreatic carcinogenesis. Pancreatic cancer was induced with 20 mg BOP/kg body wt, s.c. administered at 8 weeks of age. One week later, hamsters were assigned to one of five diet treatments: (i) 4.3% corn oil (control); (ii) 20.5% corn oil (high corn oil); (iii) 0.5% corn oil + 3.8% beef tallow (low beef tallow); (iv) 0.6% corn oil + 19.9% beef tallow (high beef tallow); and (v) 5.1% corn oil + 15.4% beef tallow (high fat mixture). These diets were fed until the study ended 84 weeks after BOP treatment. Hamsters were trained through pair feeding to consume the same calorie allotment as the control corn oil group. By the end of the experiment, BOP-treated hamsters that were fed diets containing beef tallow were consistently heavier than those fed corn oil. Survival was longer in hamsters fed the high-beef tallow and high-fat mixture compared with the other diet groups. Tumor data were age adjusted to correct for survival differences. Pancreatic adenoma incidence and multiplicity (no./effective animal) were higher in hamsters fed beef tallow than those fed corn oil diets. Carcinoma in situ multiplicity was elevated in hamsters fed high-fat diets irrespective of the nature of fat fed. Pancreatic adenocarcinoma multiplicity was elevated in hamsters fed the low- or high-beef tallow diets compared with the low- or high-corn oil diets. The mixture of fat resulted in an intermediate yield.     

Direct Effects of Testosterone, Dihydrotestosterone and Estrogen on 3,2'-Dimethyl-4-aminobiphenyl-induced Prostate Carcinogenesis in Castrated F344 Rats

The present experiment was carried out to explore the effect of endogenous androgen on rat prostate carcinogenesis induced by 3,2'-dimethyl-4-aminobiphenyl (DMAB) and testosterone propionate (TP) or 5α-dihydrotestosterone (DHT) with or without ethinyl estradiol (EE). In order to eliminate the influence of endogenous androgen, F344 rats were orchiectomized just after initiation with the prostate carcinogen, DMAB, and then given TP, DHT, TP plus EE or DHT plus EE for 40 weeks. The results demonstrated that while administration of TP following DMAB treatment causes invasive carcinomas in the lateral and anterior prostate and seminal vesicles, DHT does not exhibit equivalent effects. Synergistic enhancement was also evident with TP plus EE, but not with DHT plus EE. The incidences of prostatic and seminal vesicle lesions in all groups of the present experiment, except for the group given castration without hormonal supplement, were equivalent to those previously found in non-castrated animals. Therefore, the present findings indicate that endogenous testosterone may not be required for promotion hy TP/EE of DMAB-initiated prostate carcinogenesis and that it may not contribute to the actions of DHT.     

Induction of invasive carcinomas in the accessory sex organs other than the ventral prostate of rats given 3,2'-dimethyl-4-aminobiphenyl and testosterone propionate

The promotion effects of testosterone propionate (TP) on prostate carcinogenesis were investigated in F344 rats given the prostatic carcinogen, 3,2'-dimethyl-4-aminobiphenyl (DMAB). One group of animals received s.c. DMAB injections at a dose of 50 mg/kg body weight at 2-week intervals for a total of 10 injections along with s.c. implantations of TP-containing Silastic tubes. A second experimental group of rats was given DMAB at the same dose and intervals but each injection of DMAB was combined with 3 prior consecutive daily 100-mg/kg body weight s.c. injections of TP. After cessation of carcinogen administration, animals in these two groups received TP implants from week 21 to the end of the experiment. All surviving animals were killed at week 56 and accessory sex gland tumor incidences were compared to those in DMAB alone and other appropriate control groups. The groups given TP plus DMAB and subsequent long term administration of TP developed lesions of the dorsolateral prostate, seminal vesicles, and coagulating glands which were all invasive adenocarcinomas. Incidences were 84.2% (16 of 19 rats) and 66.7% (12 of 18 rats), respectively. Macroscopic large tumors were induced in 13 animals among which 8 demonstrated metastasis to the abdominal cavity, liver, or lung. None of the control groups except for the group given TP injections plus DMAB had equivalent tumors. Development of carcinomas of the ventral prostate, which were all of in situ type, were not increased by subsequent treatment with TP. These data thus clearly showed that TP can exert strong enhancing effects on tumor development in the dorsolateral prostate, seminal vesicles, and coagulating glands but not in the ventral prostate.     

High fat diet elevates the activity of inducible nitric oxide synthase and 1,2-dimethylhydrazine-induced aberrant crypt foci in colon of rats

Rats were examined for the effect of dietary level of fat (beef tallow or safflower oil) on colonic activity of inducible nitric oxide synthase (iNOS) which has been suggested to be associated with colon carcinogenesis. In experiment 1, feeding high fat diets (20%) for 3 weeks caused higher activity of the iNOS compared to feeding low fat diets (5%). In experiment 2, rats were fed 20% or 5% beef tallow diet for 11 or 32 days, and given an injection of a carcinogen, 1,2-dimethylhydrazine on day 4. The activity of colonic iNOS and the development of colonic aberrant crypt foci were enhanced by high fat diet.     

Lack of tumorigenic response in the prostate gland of castrated F344 rats by 3,2'-dimethyl-4-aminobiphenyl given with methyltestosterone

In an attempt to induce a high incidence of prostate carcinoma, 3,2'-dimethyl-4-aminobiphenyl (DMAB), a prostatic carcinogen, was given during the period of cell proliferation of the prostate gland induced by the administration of methyltestosterone (MT) to castrated F344 rats. Three weeks after the surgical castration, rats were given diet containing 300 ppm of MT for 2 weeks and basal for 2 weeks alternately 12 times. During each treatment with MT, one (group 1) or two (group 2) subcutaneous injections of 50 mg/kg body wt. of DMAB was given. After the last treatment of MT, a pellet of testosterone propionate (TP) was implanted in the subcutis of all animals until the end of the experiment (week 60). No carcinomas developed in the prostate gland of any of the rats. Atypical hyperplasia of the ventral lobe of prostate was found in 4 of 22 rats in group 1 and 2 of 20 rats in group 2. The incidences of atypical hyperplasia of the seminal vesicles in groups 1 and 2 were 64% and 75%, respectively. No pathological lesions in the prostate were observed in 32 rats given DMAB without MT treatment.     

Enhancing Effect of Cadmium on Rat Ventral Prostate Carcinogenesis Induced by 3,2'-Dimethyl-4-aminobiphenyl

The effects of cadmium given at different stages during 3,2'-dimethyl-4-aminobiphenyl (DMAB)-induced rat prostate carcinogenesis were investigated using male F344 rats. Animals were given 10 subcutaneous injections of 50 mg/kg body weight of DMAB or the corn oil vehicle at two-week intervals. In addition, cadmium was administered at doses of 0, 10, or 30 /μmol/kg body weight as single intramuscular injection on the 1st day of the experiment or one day after the last injection of DMAB at week 20. Two further groups were subjected to administration of cadmium at 10 μmol/kg at week 20 and then 5 μmol/kg at week 40, or 10 μmol/kg at week 20 and then 5 μmol/kg at weeks 30, 40 and 50. At the termination, 60 weeks after the beginning of the experiment, the incidences and multiplicity of ventral prostate carcinomas in the groups given cadmium plus DMAB demonstrated a consistent tendency for increase over control values (groups receiving DMAB or cadmium alone). The numbers of carcinomas per rat and per unit area of prostate section were significantly elevated in the two groups given low doses of cadmium after cessation of DMAB administration. Cadmium alone also induced a few prostate carcinomas. The influence on development of prostate tumors did not appear to be a result of the induced severe testicular atrophy because serum testosterone levels were not affected. The results indicate that cadmium and DMAB can act synergistically to cause rat prostate carcinogenesis.     

Steady state levels of transforming growth factor-beta1 and -beta2 mRNA and protein expression are elevated in colonic tumors in vivo irrespective of dietary lipids intervention

Colonic tumors of human origin produce abundant transforming growth factor (TGF)-beta suggesting that TGF-beta is critical to their growth. Dietary lipids regulate a number of growth factors including TGF-beta. Whether elevated TGF-beta levels are consistently expressed in colonic tumors irrespective of the environmental milieu in an in vivo model is not known and forms the main objective of the present study. Male F344 rats were injected with azoxymethane, 10 weeks later, rats bearing preneoplastic lesions were fed a low fat (5% corn oil) diet and 3 high fat (5% corn oil with 18% corn oil, fish oil or beef tallow) diets for 16 weeks. Colonic tumors and mucosae were processed and assessed for TGF-beta status. TGF-beta1 and -beta2 mRNA levels were upregulated in colonic tumors more than in mucosae of all diet groups. Dietary lipids modulated TGF-beta mRNA in both tumors and mucosae, high corn and fish oil diets upregulated TGF-beta1 significantly more than the low fat corn oil or high fat beef tallow diets. Immunohistochemical assessments of tissues with different biological features revealed that TGF-beta1 and -beta2 were elevated in tumors and in selected microscopic preneoplastic lesions compared to normal mucosae. This is the first in vivo study, documenting that developing colonic tumors acquire upregulated TGF-beta phenotype even in the presence of lipid environments capable of differentially regulating TGF-beta in normal mucosae. Elevated expression of TGF-beta in a selected subset of microscopic preneoplastic lesions suggests that TGF-beta plays an important role on both early and late stages of colon carcinogenesis.     

Lack of modification by naturally occurring antioxidants of 3,2'-dimethyl-4-aminobiphenyl-initiated rat prostate carcinogenesis

The modifying effects of 6 naturally occurring antioxidants on 3,2'-dimethyl-4-aminobiphenyl (DMAB)-initiated rat prostate carcinogenesis were investigated in male F344 rats. Animals were pretreated with DMAB in a 20-week initiation protocol and then administered basal diet containing 0.8% catechol, 0.8% resorcinol, 0.8% hydroquinone, 2 ppm selenium, 2% gamma-orysanol or 1% alpha-tocopherol for 40 weeks. The experiment was terminated at week 60 for histopathological assessment of lesion development. Atypical hyperplasias and carcinomas of the prostate were observed in the ventral lobe in all groups treated with DMAB. However, the incidences of these lesions were not significantly different between carcinogen control and antioxidant-treated groups. There were also no significant increases or decreases in the incidences of tumors in any other organs.     

Comparative effects of different animal and vegetable fats fed before and during carcinogen administration on mammary tumorigenesis, sexual maturation, and endocrine function in rats

The purpose of this investigation was to determine whether diets high in animal or vegetable fat affected mammary tumorigenesis when fed to rats only prior to and during the initiation phase of carcinogenesis. Weanling 21-day-old female Sprague-Dawley rats were divided into different dietary treatment groups and were allowed to feed and libitum on one of the following diets: 5% (normal fat) corn oil; 20% (high fat) corn oil; 20% palm oil; 20% beef tallow; or 20% lard. At 52 days of age, all rats were given p.o. 7.5 mg 7,12-dimethylbenz(a)anthracene (DMBA). One week following DMBA administration, all rats were switched to the 5% corn oil control diet and were maintained on this diet for the duration of the experiment. Rats fed a 20% lard diet during the treatment period showed a significant increase in mammary tumor incidence and number 19 weeks after DMBA administration, when compared to all other dietary treatment groups. Rats fed a 20% beef tallow diet during this same time period also demonstrated enhanced mammary tumor development, during the 10- to 19-week time period after DMBA. Mammary tumor development in rats fed 20% corn oil or palm oil diets during this treatment period was similar to that of normal fat controls. Estrogens are potent stimulators of mammary tumor growth and development in rats. Because mammary tumorigenesis was enhanced in rats fed high animal, but not vegetable fat diets, it was possible that estrogens present in animal fat might be responsible for this stimulation. Further studies demonstrated however, that increased mammary tumorigenesis in rats fed diets high in animal fat could not be explained on the basis of endocrine stimulation. Average day of vaginal opening for all groups fed 20% fat diets was similar and occurred earlier than in normal fat controls. In addition, 50- to 65-day-old rats in the different dietary treatment groups showed no differences in basal or surge levels of serum prolactin, luteinizing hormone, or estradiol. Rat diestrus uterine weight also showed no significant differences among dietary treatment groups. Thus diets containing high levels of animal fat caused little if any increased estrogenic activity in rats. In conclusion, high dietary intake of lard and beef tallow, but not vegetable fat, fed from weaning until only 1 week after DMBA administration, significantly enhances mammary tumorigenesis in rats. The mechanism(s) by which animal fat induces this stimulation is not clear, but it does not appear to result from endogenous or exogenous endocrine stimulation.     

Lack of chemopreventive effects of lycopene and curcumin on experimental rat prostate carcinogenesis

The chemopreventive efficacy of lycopene and curcumin with regard to prostate carcinogenesis was investigated using 3,2'-dimethyl-4-aminobiphenol (DMAB)- and 2-amino-1-methylimidazo[4,5-b]pyridine (PhIP)-induced rat ventral prostate cancer models. Three 60 week experiments with male F344 rats were carried out. In the first DMAB was given for the first 20 weeks and lycopene or curcumin were administered concomitantly or subsequently at dietary doses of 15 and 500 p.p.m., respectively. In the second experiment lycopene and curcumin were given to rats pretreated with DMAB at doses of 5, 15 or 45 p.p.m. or 100 or 500 p.p.m. In the third PhIP was selected as an initiator for prostate carcinogenesis and administered for 20 weeks. Rats were then fed a diet containing lycopene at a dose of 45 p.p.m. or curcumin at a dose of 500 p.p.m. or both together. Chemopreventive effects of lycopene and curcumin on development of DMAB-induced ventral prostate carcinomas were observed only in the first experiment and no confirmation of inhibition potential was obtained in the following studies. Neither summational nor synergistic chemoprevention was evident. It is concluded from the present data that, overall, neither lycopene nor curcumin can consistently prevent rat prostate carcinogenesis.     

Induction of invasive carcinomas of the seminal vesicles and coagulating glands of F344 rats by administration of N-methylnitrosourea or N-nitrosobis(2-oxopropyl)amine and followed by testosterone propionate with or without high-fat diet

The potential modifying effects of testosterone propionate (TP) and high-caloric high-fat diet (20% corn oil, HF) on rat accessory sex gland carcinogenesis were investigated. Male F344 rats were treated five times at 4-week intervals with N-methylnitrosourea (MNU) i.v. or N-nitrosobis(2-oxopropyl)amine (BOP) s.c., each injection following 2 weeks pretreatment with dietary ethinyl estradiol. After completion of this carcinogen administration stage, animal groups received subcutaneous implantation of Silastic tubes filled with 40 mg TP with or without HF for 40 weeks. Carcinomas of the seminal vesicles and/or coagulating glands were induced in 5, 39 and 56% of rats given MNU alone, MNU and TP, and MNU and HF plus TP respectively. No equivalent tumors were found in rats given MNU and HF. In the BOP-treated groups, 11% of animals receiving TP but no HF diet demonstrated seminal vesicle carcinomas and 6% of rats receiving TP plus HF diet had coagulating gland carcinoma. Thus while TP exerted a strong enhancing effect on tumor growth in the seminal vesicles and coagulating glands, high caloric HF did not manifest any significant influence.     

Ki-ras mutations with frequent normal allele loss versus absence of p53 mutations in rat prostate and seminal vesicle carcinomas induced with 3,2′-dimethyl-4-aminobiphenyl

We have developed a prostate carcinogenesis model in Fischer 344 rats using 3,2′-dimethyl-4-aminobiphenyl (DMAB) as a carcinogen to examine various potential modifying factors. In this study, mutational changes in the ras and p53 genes were assessed in DMAB-induced rat prostate and seminal vesicle carcinomas by single-strand conformation polymorphism analysis and subsequent direct DNA sequencing. Eight of 22 prostate adenocarcinomas (three of nine (33.3%) from the ventral lobe and five of 13 (38.5%) from the dorsolateral lobe, including three transplantable tumors) and one of 11 seminal vesicle adenocarcinomas (9.1 %) demonstrated point mutations in the Ki-ras gene. One prostate malignant fibrohistiocytoma examined was negative. Among the positive cases, five (three ventral prostate carcinomas and two transplantable tumors) also showed loss of the normal allele. In contrast, other than one mutation in the p53 gene in the malignant fibrohistiocytoma, there were no mutations in the Ha-ras or p53 genes. These results indicate that mutational activation of the Ki-ras gene, but not of the Ha-ras or p53 genes may play a mechanistic role in prostate and seminal vesicle carcinogenesis by DMAB and that a loss of the normal allele of the Ki-ras gene may also be involved in the process. © 1995 Wiley-Liss, Inc.     

Lack of modifying effects of 4-ter t-octylphenol and benzyl butyl phthalate on 3,2-dimethyl-4-aminobiphenyl-induced prostate carcinogenesis in rats

The modifying effects of dietary feeding of two estrogenic compounds, 4-tert-octylphenol (tOP) and benzyl butyl phthalate (BBP), on 3,2-dimethyl-4-aminobiphenol (DMAB)-induced prostatic carcinogenesis were investigated in male F344 rats. We also assessed the effects of the test compounds on the proliferating cell nuclear antigen (PCNA) index in induced neoplasms, prostatic intra-epithelial neoplasm (PIN), and non-lesional glands in the prostate. To induce prostatic neoplasms, rats were given subcutaneous injections of DMAB (25 mg/kg body weight) every other week, 10 times in total. They also received the experimental diet containing 10 or 100 ppm tOP and BBP for 40 weeks, starting 1 week after the last dosing of DMAB. DMAB exposure produced prostatic adenocarcinoma with an incidence of 41.2% at the end of the study (week 60). Dietary administration of tOP and BBP did not affect the incidence of prostatic adenocarcinoma: 43.8% in the DMAB --> 10 ppm tOP group; 25.0% in the DMAB --> 100 ppm tOP group; 43.8% in the DMAB --> 10 ppm BBP group; and 43.8% in the DMAB --> 100 ppm BBP group. The PCNA indices in adenocarcinomas, PIN, and non-lesional glands in rats treated with DMAB and tOP or BBP were slightly lower than that of the DMAB alone group, but the differences were not statistically significant. These results might suggest that dietary feeding of the estrogenic compounds tOP and BBP did not modulate DMAB-induced prostatic carcinogenesis in rats.     

Effects of dietary fat on hepatic microsomal and cytosolic mutagenic activation of 2-aminofluorene.

The present study was designed to examine the effects of different high fat diets on the liver microsomal and cytosolic mutagenic activation of 2-aminofluorene. Male Sprague-Dawley rats were fed either a low fat (5% corn oil) or high fat (20%) diets containing either corn oil (CO), menhaden oil (MO) or beef tallow (BT). After 2 weeks on the test diets, animals from each group were placed on a protocol of weekly injection with 1,2-dimethylhydrazine dihydrochloride (DMH) for 10 weeks. Animals were given DMH injections i.p. and killed 3 h after injection following 5 and 10 DMH treatments. The metabolic activity of liver microsomes and cytosol was assessed by the Ames test using 2-aminofluorene as a standard mutagen. Beef tallow-fed rats had the highest microsomal mutagenic activation, followed by the basal diet. Decreased liver microsomal and cytosolic metabolism of the reference mutagen was detected in the MO and CO diets compared to basal or BT diets. However, there was an increased activity in MO and CO fed groups after week 10, while beef tallow showed a slightly decreased activation. These data indicate that type of dietary fat affects liver microsomal mutagenic activation of carcinogens.     

Development of Androgen-independent Carcinomas from Androgen-dependent Preneoplastic Lesions in the Male Accessory Sex Organs of Rats Treated with 3,2'-Dimethyl-4-aminobiphenyl and Testosterone Propionate

Two kinds of cancer can be induced in rat male accessory sex organs, one a non-invasive carcinoma arising in the ventral lobe and the other an invasive lesion which develops in the dorsolateral and anterior lobe as well as the seminal vesicles. In the present study, one group of male rats were given biweekly s.c. injections of 3,2'-dimethyl-4-aminobiphenyl (DMAB) for 20 weeks for induction of non-invasive carcinomas and the other group received DMAB with 40-week testosterone propionate for induction of invasive carcinomas. Half of the animals in each group were then subjected to bilateral orchiectomy at week 41 to remove testicular androgen, in order to examine the androgen dependence of both types of carcinomas as well as precancerous lesions. Animals were killed at weeks 41, 46 and 60. All parts of the prostate complex showed involution and significant weight reduction after castration, with a complete disappearance of atypical hyperplasias and carcinomas of the ventral prostate. However, in spite of suppression of development of atypical hyperplasias in the anterior prostate and seminal vesicles, the incidence of invasive carcinomas was not changed. Normal epithelial cells and atypical hyperplasias of all parts of the prostate and seminal vesicles and carcinomas of the ventral prostate were immunohistochemically positive for nuclear androgen receptor, while invasive carcinomas that developed in either castrated or non-castrated animals were negative. These findings suggest that in the ventral prostate, both precancerous and cancerous lesions are androgen-dependent, but in the anterior and seminal vesicles, cancerous lesions (invasive carcinomas) are androgen-independent while precancerous lesions are hormone-dependent.