摘要:

Mammary tumors develop earlier and in greater numbers in C3H mice fed diets containing up to 1000 ppb diethylstilbestrol or 5000 ppb estradiol‐17ß. We have analyzed the steroid‐hormone‐binding proteins in cytosols of normal target tissues and in neoplastic mammary tissues of control and estrogen‐fed mice to determine whether the capacity for hormone response was altered by dietary estrogens. Using estradiol‐17β as a ligand, estrogen‐binding proteins were measured with Kd= 10−11−10−10M and sedimentation constants of 8 and 4 S. The binding capacity (per mg cytosol protein) of uterus exceeded that of normal mammary gland 10–20‐fold, while mammary tumors only contained half the binding capacity of virgin mammary gland. Binding proteins for the glucocorticoid, triamcinolone acetonide, exhibited a sedimentation constant of 7–8 S and Kd= 10−9−10−8M. The glucocorticoid binding capacity of mammary tumors exceeded that of virgin mammary gland. Binding proteins for progestins were measured using the synthetic ligand R5020. Mammary gland contained progestin‐binding proteins with 4 S sedimentation constants and Kd— 10−9−10−8M. Not all mammary tumors contained progestin‐binding proteins, and the binding capacities varied considerably among those that did. The molecular characteristics of the steroid receptors in tumors were the same as those found in normal target tissues. There was nothing to suggest that dietary estrogens altered the characteristics of the three steroid‐binding proteins.

ISSN:0098-4108    

DOI:10.1080/15287398309530412

出版商:Taylor & Francis Group    

年代:1983

数据来源: Taylor

摘要:

This present study was designed to assess the role of metabolic and pharmacokinetic factors in the lower susceptibility of female rats compared to male rats to xenobiotics metabolized by the cytochrome P‐450‐dependent mixed‐function oxidase (MFO) system. Adult intact male and female Sprague‐Dawley rats were administered labeled acetaminophen (1 g/kg body weight + 5 μCi [3H]acetaminophen) after an overnight fast. They were bled and killed at 0.5, 7, 2, 3, 6, 12, 24, and 36 h after drug administration. The percentage of [3H]acetaminophen radioactivity remaining in blood, liver, GI tract, and excreted in the urine was determined at all time intervals. Plasma prothrombin time and serum transaminases were determined as indices of hepatotoxicity. Hepatic GSH and glycogen were assayed. Total urinary acetaminophen and its metabolites and the molar percent of various metabolites excreted during the first 6 h were determined. Castrated male and ovariectomized female rats and their respective controls were also given acetaminophen (APAP) and were killed 24 h later to determine hepatotoxicity. The extent of hepatic damage in the intact male rats was greater and appeared sooner than in the female rats. Hepatic GSH and glycogen were depleted earlier in female rats. The percent of the administered dose excreted in the urine during the first 6 h was 17.5 for the male rat versus 24.5 for the female rat. While the APAP glucuronide conjugate concentration was significantly higher, the APAP sulfate conjugate concentration was lower in the female than it was in the male rat. Although peak radioactivity in serum was reached by 30 min in both male and female rats, suggesting quick intestinal absorption, it was significantly higher in female rats and was associated with decreased intestinal and hepatic levels and increased urinary excretion when compared to male rats. While castration of male rats decreased susceptibility to hepatotoxicity, ovariectomy of female rats tended to increase susceptibility to hepatotoxicity in comparison to their respective controls.

ISSN:0098-4108    

DOI:10.1080/15287398309530413

出版商:Taylor & Francis Group    

年代:1983

数据来源: Taylor

摘要:

The commonly used plasticizer di(2‐ethylhexyl) phthalate (DEHP) was recently tested for chronic toxic potential by incorporation into the diet of rats and mice for approximately 2 yr. Upon reviewing the test results, the sponsoring organization concluded that DEHP was carcinogenic to the rats and mice, as indicated by increased occurrences of liver tumors in the DEHP‐exposed animals in comparison to controls. Another group has disagreed with this conclusion, however, citing perceived methodological deficiencies and improper interpretations in the study, and has also suggested that rodents may not be adequate models of human response to DEHP. This communication compares the conduct of the DEHP bioassay favorably with state‐of‐the‐art procedures in animal carcinogenicity testing and documents approval of the study Interpretations by several independent peer review groups. The carcinogenic potential of DEHP is placed in perspective by evaluating the evidence for DEHP‐induced tumors in rodent species in light of dose response relationships, other biochemical and toxicological effects of DEHP, and its comparative metabolism and disposition in rodent and primate species. A composite analysis of the currently available information indicates that DEHP has been shown to be carcinogenic to rodents in a valid chronic test, indicating that it should be considered as a potential carcinogen in humans, as well. Further experimental inquiry will be required, however, to accurately assess the potential health risks posed to humans by exposure to small amounts of this plasticizer.

ISSN:0098-4108    

DOI:10.1080/15287398309530414

出版商:Taylor & Francis Group    

年代:1983

数据来源: Taylor

ISSN:0098-4108    

DOI:10.1080/15287398309530401

出版商:Taylor & Francis Group    

年代:1983

数据来源: Taylor