Alterations in epidermal growth factor binding to hepatic membranes following dietary exposure of rats to known hepatocarcinogens

Administration of the chemical carcinogen 2-acetylaminofluorene (2-AAF) has previously been shown to lower hepatic epidermal growth factor (EGF) binding levels during chemically induced hepatocarcinogenesis. To further characterize the specificity of this response, EGF binding levels for liver microsomes were determined after a 3-week administration of subacute doses of 2-AAF and five other known hepatocarcinogens: 3′-methyl-4-dimethylaminoa-zobenzene (3′Me-DAB), 2-AAF, aflatoxin B₁ (AFB1), thioacetamide (TA), ethionine, benzidine (Benz), as well as four non-hepatocarcinogeos: fluorene, p-aminoazobenzene, 4-acetylaminofluorene (4-AAF), and 3-methylcholanthrene. Five of six of the hepatocarcinogens tested (3′Me-DAB, 2-AAF, TA, AFB1 and Benz) caused significant lowering of EGF binding levels, and one of the four non-hepatocarcinogens (4-AAF) caused significant lowering of EGF binding levels. Paired feeding studies indicated that the decreases in EGF binding levels were not a result of differences in net diet consumption. These findings show that decreases in EGF binding capacity are caused by a diverse group of known hepatocarcinogenic compounds at an early stage in the carcinogenesis process.     

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) modulates epidermal growth factor (EGF) binding to basal cells from a human keratinocyte cell line

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) modulates the proliferation, differentiation, or both, of epidermal keratinocytes in vivo and in culture. The growth of epidermal cells in culture is regulated by several biochemical mediators including epidermal growth factor (EGF). In this report the actions of TCDD on EGF binding in a basal cell population from a human keratinocyte cell line were examined. TCDD decreased the specific binding of 125I-EGF to basal cells by 40% within 96 hr. This reduction in EGF binding could not be attributed to changes in the state of differentiation as assessed by cell size and morphology, and cornified envelope competence, a marker of terminal differentiation. Modulation of EGF binding by TCDD was concentration-dependent (EC50 = 1 nM) and stereospecific, suggesting involvement of the Ah receptor. Scatchard analysis of EGF binding to the basal cells indicated a single class of high-affinity sites in both control (Kd = 0.14 nM) and treated (Kd = 0.11 nM) cultures and confirmed a decrease in the number of these sites in response to TCDD. The reduction in EGF binding correlated with a decrease in EGF-stimulated DNA synthesis and cell proliferation. Comparison of differentiation-competent squamous cell carcinoma (SCC) lines treated with TCDD supported an association between modulation of EGF binding and enhanced differentiation. The data indicate that basal cells are a target for TCDD. We propose that the modulation of EGF binding in basal keratinocytes by TCDD is one of the critical regulatory events resulting in enhanced differentiation.     

Effects of TCDD on vitamin A status and liver microsomal enzyme activities in a TCDD-susceptible and a TCDD-resistant rat strain

To investigate the relationship between vitamin A status and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) lethality, the influence of TCDD on tissue and serum vitamin A levels was determined in the most TCDD-susceptible (Long-Evans) and the most TCDD-resistant (Han/Wistar) rat strains. The TCDD LD50 values of these two strains differ by a factor of more than 300. Groups of three rats per strain were used in a dose-response study (given single ip doses of 0, 4, 40, 400, 800 or 1600 micrograms TCDD/kg body weight and killed on day 11) and in a time-course experiment (given single ip doses of 0, 4 and, in the case of Han/Wistar rats only, 1600 micrograms TCDD/kg body weight, and killed on days 4, 11, 23, 50 and 76). The strains showed similar response over the 76-day study with respect to vitamin A levels in the liver, kidneys, testicles and serum after exposure to a sublethal dose of TCDD (4 micrograms/kg body weight). In contrast, TCDD doses lethal to the Long-Evans strain only (40-1600 micrograms/kg, day 11) markedly increased kidney and serum vitamin A levels in Han/Wistar rats, while they were practically without effect in Long-Evans rats. Hepatic cytochrome P-450 concentration, and the activities of 7-ethoxyresorufin O-deethylase, ethylmorphine N-demethylase, and uridine diphosphate glucuronosyltransferase (towards p-nitrophenol) were affected by the TCDD doses in much the same manner in both strains. These findings show that the correlations between TCDD lethality and changes in vitamin A status found among species of laboratory animals do not hold for Long-Evans and Han/Wistar strains of rat.     

Effects of a single exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on macro- and microstructures of feeding and drinking in two differently TCDD-sensitive rat strains

In rats, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes anorexia that may lead to fatal wasting but has hitherto been poorly characterized. Therefore, we studied in-depth feeding and drinking behaviors of TCDD-sensitive L-E rats for 5 (100 μg/kg; lethal dose) or 10 (10 μg/kg; sublethal) days and of TCDD-resistant H/W rats for 14 (100 or 1000 μg/kg; both sublethal) days postexposure to TCDD. The 1000-fold higher resistance of H/W rats to acute lethality of TCDD results from a mutation in their AH receptor (AHR). We split days into four (morning, daytime, evening, and night) or two (light/dark) circadian periods and took the repeated nature of the data into account. In L-E rats at 100 μg/kg, the feed intake dropped precipitously, due to reduced meal sizes. In H/W rats, the hypophagia remained moderate and stemmed from a reduced meal frequency. While the suppression in L-E rats peaked during the morning (at 100 μg/kg), the main effects in H/W rats were seen during the constant light or dark phases. Furthermore, chronologic data analysis revealed alterations in consecutive feeding and drinking patterns. Thus, striking differences were found between these strains in the timing and structure of consummatory behaviors, suggesting involvement of the AHR in these behaviors.     

二甲双胍对人肝癌Hep-G2细胞表皮生长因子及其受体表达的影响

目的 观察二甲双胍对人肝癌Hep-G2细胞表皮生长因子（EGF）及其受体（EGFR）的影响.方法 体外培养人肝癌Hep-G2细胞,用不同浓度二甲双胍进行干预,3-（4,5-二甲基噻唑-2）-2,5-二苯基四氨唑溴盐法检测二甲双胍对Hep-G2细胞生长的影响;Hoechst 33342染色荧光显微镜观察细胞的形态学变化,流式细胞术观察细胞凋亡;蛋白质印迹法（Western blot）检测EGF、EGFR的表达.结果 二甲双胍对肝癌细胞的活性具有明显的抑制作用,且呈剂量依赖性;以10 mmol/L作用终浓度抑制效果最明显,其48 h的细胞吸光度为（0.477 ±0.025）,与对照组（0.602±0.026）比较差异有统计学意义（P＜0.01）;逐渐增加二甲双胍的作用浓度,细胞凋亡率随之逐渐增加,药物组细胞凋亡率分别为（10.76±0.96）％、（20.77±1.16）％,与对照组（5.21±0.13）％相比差异均有统计学意义（P＜0.05）;Hoechst33342染色可见明显的细胞皱缩,核染色质浓缩,核碎裂等凋亡形态学变化;Western blot结果显示,EGF及其受体蛋白的表达随着二甲双胍作用浓度的增加而逐渐下调.结论 在体外,二甲双胍能够抑制人肝癌Hep-G2细胞增殖及诱导细胞凋亡,其抗肿瘤机制可能与细胞内EGF及EGFR表达下调有关.     

Metabolism of a tetraphenyltin compound in rats after a single oral dose

The metabolism of tetraphenyltin in rat liver and kidney has been examined. Tetraphenyltin and its metabolites in the tissue were determined periodically for 96 h after a single oral dose of 55.4 mg kg(-1) of tetraphenyltin by gas chromatography. The gas chromatographic method was able to determine simultaneously both inorganic tin and phenyltin compounds. Although initial (at 24 h) levels of tetraphenyltin in the liver approximated four times those in the kidneys, the levels of tetraphenyltin decreased more rapidly with time than those in the kidneys. These findings show that the tetraphenyltin accumulated more rapidly and highly in the liver, but was metabolized faster than that in the kidney. The levels of total tin in the liver 24 h after treatment were distinctly lower than those of di- or triphenyltin treatments in our previous studies and none of the animals showed characteristic symptoms. The toxic potencies of organotins generally correlate with accumulation of the chemicals. These results imply that the slight toxicities of tetraphenyltin might be due to the relatively low uptake of tin compounds after ingestion. The highest tin concentration among the metabolites of tetraphenyltin in the tissue, especially in liver, was observed as diphenyltin throughout the time period studied. These results suggest that part of the administered tetraphenyltin may cause some harmful effects as diphenyltin in rats, and this must be taken into consideration in toxicological research on tetraphenyltin.     

Decrease in the number of receptors for epidermal growth factor in the liver of D-galactosamine-intoxicated rats

Hepatic transport of epidermal growth factor (EGF) was studied in D-galactosamine-intoxicated rats by the multiple-indicator dilution (MID) method. The extraction ratio of 125I-labeled EGF in the intoxicated rats, obtained from a model-independent analysis of the dilution curves, decreased to 45% of the control values. A distributed two-compartment model was fitted to the dilution data by nonlinear least-squares regression, and the kinetic parameters, kon.PT (product of on-rate constant and receptor density), koff (off-rate constant) and ks (sequestration rate constant) were determined. The values of kon.PT and ks in the intoxicated rats decreased to approximately one-half and one-third of those in the control rats respectively. Similar decreases in the kon.PT and ks values in the intoxicated rats were also observed for the transport of 125I-labeled insulin, a positive control, into the liver. The 125I-labeled EGF binding experiment at equilibrium using liver homogenates revealed that the intoxication reduced the receptor density (PT) to one-third of the control values, whereas the equilibrium dissociation constant (kd) did not change significantly. The activities of Na+,K+-ATPase, cytochrome P-450 and glutathione S-transferase decreased in the intoxicated rats to 70-80% of the control values. The number of nuclei per unit area of tissue slices was also reduced to 70% of the control. Thus, the extent to which the enzyme activities and the number of nuclei decreased in the intoxicated liver was smaller than that of the number of EGF receptors. It is concluded that the reduction of EGF receptors cannot be explained by the "intact hepatocyte hypothesis" but rather by the functional change of hepatocytes induced by the administration of D-galactosamine.     

Absorption and disposition of cobalt naphthenate in rats after a single oral dose

The absorption and disposition of inorganic cobalt salts after oral administration have not been completely characterized. The objective of this project was to investigate the absorption and disposition of cobalt naphthenate in Fischer 344 rats following a single oral dose. Cobalt naphthenate was given orally at 3 doses: 0.333, 3.33, or 33.3 mg Co(II)/kg. Tissues, urine, and feces were collected over a 36-h period from the low- and high-dose groups; blood was collected from all 3 dose groups. The majority of the dose in both the low- and high-dose groups was excreted in the feces (42% and 73.1%, respectively), indicating that cobalt was incompletely absorbed from the gastrointestinal tract following oral dosing. The percent of the dose excreted in the urine was similar for low and high doses (31.8% and 26.3%, respectively). Cobalt concentrations were found to be highest in the liver and kidneys. The blood versus time cobalt concentration curves for the low-dose, intermediate-dose, and high-dose groups were elevated 4- to 5-fold, 14- to 25-fold, and 25- to 60-fold over control blood levels, respectively. The peak plasma concentrations of 0.6 and 1.7 microg Co(II)/ml occurred at approximately 4.3 h for the intermediate-dose group, and 3.3 h for the high-dose group. The terminal elimination half-lives were 24.7 and 24 h for the intermediate- and high-dose groups, respectively. Thus, although the extent of cobalt absorption as indicated by the blood concentrations and areas under the blood-time curves was not proportional to dose, the calculated pharmacokinetic values for the time to peak blood concentration and the apparent elimination rate constants were independent of dose. The amount excreted in the urine was also proportional to the dose. These apparent anomalies were not related to protein binding in blood.     

Lung growth in mice after a single dose of butylated hydroxytoluene.

In male Swiss-Webster mice, a single injection of butylated hydroxytoluene (BHT) produced a dose-dependent increase in lung weight. Histopathological changes were well developed 3 days after 500 mg/kg of BHT. After 5 days, there seemed to be a proliferation of many alveolar cells, formation of giant cells, and macrophage proliferation. Lower doses of BHT produced similar, although less extensive changes. The histopathologic alterations were accompanied by biochemical changes: 2 days after BHT, there was a significant increase in lung weight and total amounts of DNA, RNA, and protein. The changes were dose-dependent and the smallest effective dose was 250 mg/kg of BHT. Five days after BHT, the highest doses of BHT (500 and 1000 mg/kg) produced a 1.5- to 2-fold increase in lung weight, total DNA, and protein, and a 3- to 4-fold increase in total pulmonary RNA. The incorporation of thymidine into DNA and of leucine into protein increased from 2 days on after BHT. On the other hand, the incorporation of orotic acid into total pulmonary RNA was lower in the treated animals than in the controls. Administration of a single dose of BHT might offer a convenient tool to study the biochemical changes preceding and/or accompanying stimulated cell growth in lung.     

Serum methanol concentrations in rats and in men after a single dose of aspartame

Serum methanol concentrations were measured in rats and in humans given oral aspartame. The dose given to rats was the FDA's projected 99th percentile daily intake for humans, assuming aspartame were to replace all sucrose sweeteners in the diet (34 mg/kg). Four male adult volunteers each received 500 mg, equivalent to 6-8.7 mg/kg, which is approximately the FDA's estimate of mean daily human consumption. Both treatments caused a rise in serum methanol. In rats the mean peak value was 3.1 mg/litre 1 hr after administration; serum methanol returned to endogenous values 4 hr after treatment. In the men, the mean rise over endogenous values was 1.06 mg/litre after 45 min. Two hours after treatment, serum methanol had returned to basal levels. The temporary serum methanol increase showed peak values within the range of individual basal levels.     

Regulation of epidermal growth factor binding in a human keratinocyte cell line by 2,3,7,8-tetrachlorodibenzo-p-dioxin

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) decreased the binding of epidermal growth factor (EGF) by the human keratinocyte cell line SCC-12F. This response was concentration dependent (half-maximal effective concentration, EC50 = 1.8 nM) and stereospecific. Scatchard analysis of EGF binding indicated that treatment with TCDD resulted in a loss of high-affinity (Kd = 0.28 nM) binding sites. This loss was accompanied by a concomitant inhibition of EGF-stimulated DNA synthesis. The kinetics for the decrease of EGF binding by TCDD and benzo[a]pyrene (BP) were compared. Inhibition of EGF binding by BP was maximal by 24 hr, with 90% recovery of EGF binding apparent by 48 hr. In contrast, TCDD treatment for 72 hr was required to produce maximal inhibition, and no recovery was evident up to 10 day after removal of TCDD from the growth medium. The data indicate that modulation of EGF binding by TCDD was mediated by the Ah receptor. Subsequent cellular responses, for example, inhibition of EGF-stimulated DNA synthesis, may be important in the expression of altered differentiation patterns observed in human epidermal keratinocytes exposed to TCDD.     

Differences in the distribution of methyl mercury in erythrocytes,plasma, and brain of Japanese quails and rats after a single oral dose

Distribution of a single oral dose of methyl mercury (10 mg Hg/kg body weight) was followed from 90 min up to 120 h in plasma, erythrocytes, and brain of Japanese quails and rats. Significantly higher Hg concentrations were observed in plasma and brain of quails and red blood cells of rats. Blood/brain ratio decreased in quails from 6 to 2 at 24 h and 120 h respectively, whereas it increased in rats. Erythrocyte/plasma ratio in quails was about three times lower and averaged 54. The differences in Hg distribution were accompanied by a more than 3-fold higher acute toxicity in quails under adequate experimental conditions.     

TCDD decreases rapidly and persistently serum melatonin concentration without morphologically affecting the pineal gland in TCDD-resistant Han/Wistar rats.

The highly toxic environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was recently reported to decrease serum melatonin levels throughout the circadian cycle in the most TCDD-susceptible strain of rat, Long-Evans. To find out whether this effect is related to the mechanism of acute lethality of TCDD, serum melatonin levels were measured at the nocturnal peak phase in the most TCDD-resistant rat strain variant, Han/Wistar rats, 6 hr to 28 days after TCDD exposure. The same dose as used in the previous study, 50 micrograms/kg, decreased serum melatonin levels to approximately half the control values by the first day after the treatment. Melatonin concentrations remained at this reduced level over the whole observation period. In an auxiliary experiment, Han/Wistar rats were dosed with 1000 micrograms/kg TCDD and killed on day 3. Neither light nor electron microscopic examination of their pineal glands revealed any alteration attributable to TCDD treatment. These findings might indicate that the reduction of serum melatonin levels in the rat by TCDD is not related to its lethal effect and is not due to a direct damage of the pineal gland.     

Differences in DNA-guanine alkylation between male Sprague-Dawley rats and Syrian hamsters following exposure to a single dose of pancreatic nitrosamine carcinogens

N-Nitrosobis(2-oxopropyl)amine (BOP) and N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine (HPOP) are potent pancreatic carcinogens for the Syrian hamster, while in rats they primarily target the esophagus and respiratory tract. Both species metabolize these carcinogens to yield methylating and 2-hydroxypropylating agents. Ratios of N7-methylguanine (N7-MeG) to N7-(2-hydroxypropyl)guanine (N7-HPG) in hepatic DNA of BOP- and HPOP-treated hamsters are 84 and 7, respectively. Similar ratios are observed in DNA of rat liver and hamster kidney, while in the lung and pancreas of both species and also in rat kidney, such ratios are significantly lower. Differences between hamsters and rats regarding the extent of DNA alkylation are observed with either BOP or HPOP. At 50 mg/kg BOP levels of N7-MeG are 3428, 1907, 457, and 260 mumol/mol of guanine in hamster liver, kidney, lung, and pancreas, respectively. In rats treated with the same dose of BOP, levels of this adduct in corresponding tissues are 4616, 451, 372, and 105 mumol/mol of guanine. HPOP like BOP alkylates kidney and pancreas DNA more extensively in hamsters than in rats while levels of N7-MeG in liver and lung DNA are similar in both species. Levels of the O6-methylguanine (O6-MeG) are 3.6 and 5.5 times greater in the DNA of hamster pancreas than in that of the rat after an injection of 50 mg/kg BOP and HPOP, respectively. Such differences suggest that initial alkylation of hamster pancreas is a critical factor in the induction of pancreatic cancer in this species by the above nitrosamines.(ABSTRACT TRUNCATED AT 250 WORDS)     

Expression of epidermal growth factor, transforming growth factor-alpha and epidermal growth factor receptor in thyroid tumors.

Immunohistochemical study of epidermal growth factor (EGF), epidermal growth factor receptor (EGFR) and transforming growth factor-alpha (TGF-alpha) expression was performed on paraffin-embedded tissue specimens of 12 follicular carcinomas, 15 papillary carcinomas and 15 adenomas of the thyroid gland. The tumors were placed in one of the following eight groups, according to the results of EGF, TGF-alpha and EGFR expression: group 1: none, group 2: only EGFR, group 3: EGFR and TGF-alpha, group 4: EGFR and EGF, group 5: TGF-alpha, and EGF, group 6: all three, group 7: only TFG-alpha and, finally, group 8: only EGF. Statistical analysis of the results revealed that the ratio of thyroid carcinomas with lymph node metastasis was significantly higher in groups 3 and 6 for follicular carcinomas (P less than 0.01) and in groups 4, 5 and 6 for papillary carcinomas (P less than 0.01). These results suggest that thyroid carcinomas expressing the systems EGF/EGFR, TGF-alpha/EGFR or TGF-alpha/EGF/EGFR display pathologic features of more aggressive disease. Furthermore, the synchronous expression of EGF, TGF-alpha and EGFR indicates that these carcinomas may regulate their growth by an autocrine and/or paracrine mechanism.     

Decreased ligand binding to the hepatic glucocorticoid and epidermal growth factor receptors after 2,3,4,7,8-pentachlorodibenzofuran and 1,2,3,4,7,8-hexachlorodibenzofuran treatment of pregnant mice

2,3,4,7,8-Pentachlorodibenzofuran (PeCDF) and 1,2,3,4,7,8-hexachlorodibenzofuran (HCDF) are environmental contaminants which mimic many of the toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Like TCDD, these polychlorinated dibenzofurans (PCDFs) induce hepatic benzo[a]pyrene hydroxylase activity (BPH) and possess high affinity for the Ah receptor. Another similarity of these PCDFs to TCDD is their ability to induce teratogenic effects such as cleft palate and hydronephrosis in mice. Recent studies have shown that TCDD modifies the equilibrium binding kinetics of the rat liver cytosolic glucocorticoid receptor (GRc) and the hepatic plasma membrane epidermal growth factor (EGF) receptor. To gain a better understanding of the action of halogenated hydrocarbons on these cytosolic and membrane-bound receptor systems during pregnancy, we investigated the biochemical effects of PeCDF and HCDF on the binding kinetics of maternal mouse liver GRc and EGF receptors and the induction of BPH activities. Pregnant C57BL/6N mice were treated once daily on gestation Days 10 through 13 with PeCDF (0-30 micrograms/kg) or HCDF (0-300 micrograms/kg). Hepatic [3H]dexamethasone and [125I]EGF equilibrium binding studies indicated that all doses of PeCDF tested (10, 20, and 30 micrograms/kg) significantly reduced the GRc and EGF receptor maximum binding capacities but did not affect the binding affinities of these receptors when compared to corn oil-treated control pregnant mice. Similar effects were observed for doses of HCDF greater than or equal to 100 micrograms/kg. These data suggest that the dibenzofuran-mediated decreases in GRc and EGF receptor binding capacities are similar to those caused by TCDD. Although the mechanism of action is not yet clear, our results indicate that halogenated aromatic compounds in addition to TCDD have profound effects on both steroid and growth factor receptor systems.     

Dose-dependent elevation of Ah receptor binding by TCDD in rat liver

Changes in [3H]TCDD binding to unoccupied liver Ah receptor were examined following chronic or acute administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to adult female Sprague-Dawley rats. Chronic biweekly administration of TCDD equivalent to 0, 10, 30, or 100 ng/kg/day TCDD for 22 weeks caused dose-dependent increases in liver TCDD concentration, aryl hydrocarbon hydroxylase (AHH) induction, and [3H]TCDD binding to unoccupied cytosolic Ah receptor sites. Maximal increases (twofold) of cytosolic receptor binding occurred at an estimated dose of slightly greater than 30 ng/kg/day. The increase in [3H]TCDD binding was half-maximal at an estimated dose of approximately 17 ng/kg/day which produced a liver concentration of 1.5 ppb TCDD. Cytosolic [3H]TCDD binding in control and treated animals sedimented mainly in the 8-9 S region of sucrose density gradients with a minor peak sedimenting in the 4-5 S region. Binding was markedly elevated in the 8-9 S region of cytosols from the TCDD-induced rats; however, TCDD treatment had no affect on [3H]TCDD binding in the 4-5 S region. Saturation and Scatchard analyses of Ah receptor binding showed no apparent changes in Kd following chronic TCDD treatment; however, a twofold increase in the number of unoccupied Ah receptor binding sites was observed. Neither aging nor ovariectomy significantly changed measurable cytosolic Ah receptor binding in control animals. When adult female rats were administered a single dose of TCDD (6 micrograms/kg) an initial drop (approximately 40%) in cytosolic receptor binding was observed at 30 and 60 min, followed by a steady increase in binding up to 250% of controls 9 days after TCDD treatment.     

Long-term effects of a single oral dose of polybrominated biphenyls on serum and liver lipids in rats

Adult (5 months) male Sherman strain rats received a single dose of either 0 or 500 mg polybrominated biphenyls (PBB) in corn oil/kg body weight by stomach tube. After an 18-month recovery period, serum and liver samples were examined. The primary serum lipid response was an increase in cholesterol (both free and esterified) and in total phospholipids. The percentage of esterified cholesterol was not significantly different from that of the controls, and no significant differences in the cholesterol ester fatty acid composition were observed. Serum triglycerides were also unaffected. In the PBB-dosed animals, the total hepatic fatty acids contained significantly less palmitic acid and more stearic acid, consistent with an increase in palmitic acid chain elongation activity. No significant differences could be detected in the n-3 or n-6 acids except for a slight decline in the content of 22:6 (n-3). Hepatic microsomal phospholipids were slightly higher (per milligram protein) in the PBB-dosed animals, and the cholesterol content was lower. Consequently, the cholesterol-phospholipid ratio was reduced, and microsomes from the latter group appeared to have an altered lipid domain on the basis of steady-state fluorescence anisotrophy measurements. In addition, total hepatic thiobarbituric acid-reactive substances (assayed as malondialdehyde) were significantly increased in the PBB-dosed animals. This observation appeared to reflect an increased susceptibility to peroxidative stress in the latter group, probably resulting from reduced membrane antioxidant concentrations. The PBB-dosed rats had significantly lower serum retinol levels and a reduced content of this vitamin in liver microsomes. Microsomes were also deficient in alpha-tocopherol in the PBB-dosed animals, although serum levels were normal.     

重组人表皮生长因子对实验性大鼠子宫颈炎的治疗作用

重组人表皮生长因子 (recombinant human epidermal growth factor, rhEGF) 对消化性溃疡、溃疡性结肠炎和角膜炎等具有明显疗效[1].本文研究rhEGF对子宫颈炎的疗效及部分机制.