Multigenerational exposure to ethinyl estradiol affects bone geometry, but not bone mineral density in rats.

Estrogenic compounds are known to prevent bone loss in ovariectomized adult rats; however, their effects on bone in developing and reproductively-intact rats are less well-understood. In a large multigenerational experiment 0, 2, 10, or 50 ppb ethinyl estradiol (EE) in the diet was fed to intact male and female rats from conception until either weaning, postnatal day 140, or continuously for 2 years. Vertebrae (lumbar and caudal) and femurs were collected from subsets of these animals at necropsy at 48 days, 70 days, 140 days, or 2 years of age and subjected to dual-energy X-ray absorptiometry (DXA) scanning to measure bone mineral density (BMD), bone mineral content (BMC), and bone area.

Multigenerational exposure to genistein does not increase bone mineral density in rats.

Genistein has been shown to prevent bone loss in ovariectomized adult rats. However, the effects of genistein on bone in developing and reproductively-intact rats have not been examined. A large multigenerational experiment involved feeding 0, 5, 100, or 500 ppm genistein in the diet to intact male and female rats from conception until either weaning, postnatal day 140, or continuously for 2 years.

Dietary modulation of 7,12-dimethylbenz[a]anthracene (DMBA)-induced adrenal toxicity in female Sprague-Dawley rats.

In this study, dietary modulation of 7,12-dimethylbenz[a]anthracene (DMBA)-induced adrenal toxicity in rats was investigated. Beginning at postnatal day (PND) 21, female Sprague-Dawley rats were fed either soy-containing NIH-31 diet or soy- and alfalfa-free 5K96 diet. On the first day of diestrus when the animals were PND 50 +/- 5, rats received either an oral dose of 80 mg/kg DMBA or sesame oil, the vehicle, and were sacrificed at 24, 36, or 48 h after treatment.

Effects of dietary soy and estrous cycle on adrenal cytochrome p450 1B1 expression and DMBA metabolism in adrenal glands and livers in female Sprague-Dawley rats.

Cytochrome p450 1B1 (CYP1B1) has been shown to be important in the bioactivation of 7,12-dimethylbenz[a]anthracene (DMBA) to an adrenal toxin in rats. We investigated the effects of diet and stage of estrous cycle on CYP1B1 expression in rat adrenal glands and on DMBA metabolism by rat adrenal and hepatic microsomes. Female Sprague-Dawley (SD) rats were placed on either standard soy-containing NIH-31 rat chow or soy- and alfalfa-free 5K96 diet from postnatal day (PND) 21 until sacrifice at PND50+/-5.

Estrogen receptor expression in the prostate of rats treated with dietary genistein.

Steroid hormones and their receptors play critical roles in the growth, development, and maintenance of the male reproductive tract. Genistein, a naturally occurring isoflavonoid primarily found in soybeans, interacts with estrogen receptors alpha and beta (ER alpha and beta), with preferential affinity for ER beta. This is one mechanism whereby genistein may affect growth and development and potentially alter susceptibility to carcinogenesis.

Effect of nonylphenol on serum testosterone levels and testicular steroidogenic enzyme activity in neonatal, pubertal, and adult rats.

Previous dose range-finding studies with nonylphenol (NP) administered to rats in a soy- and alfalfa-free diet showed apparent feminization of several endpoints in male rats at doses of 25 ppm and above. One possible mechanism contributing to these effects is a reduction of testosterone at critical developmental periods. The present study was conducted as an adjunct to a multigeneration study and was designed to examine the effect of NP on testosterone production.

A comparison of the inflammatory response to a polydimethylsiloxane implant in male and female Balb/c mice.

The implantation of biomaterials elicits a host response that influences the long-term behavior of implanted medical devices. This foreign body response is governed by cells of the immune system. Because sexual dimorphism in the immune system is well-established, a comparative study of the foreign body response in male and female mice was initiated.

Differences in the response to oxidative stress and mutant frequency in CD (Sprague-Dawley) and Fisher 344 rats due to an induced inflammatory response.

In this study, the rodent air pouch model was used to examine the production and processing of oxidative DNA damage in two strains of rats commonly used in toxicity testing. An inflammatory response was induced by injecting zymosan A (50 mg) into an air pouch on male CD (Sprague-Dawley [S-D]) and Fisher 344 (F-344) rats, and the animals were then sacrificed at 1, 3, 7, 14, and 28 days (n = 6 per time point per strain). Tissues from the lining of the air pouch were collected for 8-hydroxy-2'-deoxyguanosine (8-OH-dG) analysis and for paraffin embedding.

Metabolism and DNA binding of the environmental colon carcinogen 6-nitrochrysene in rats.

The environmental contaminant 6-nitrochrysene (6-NC) has been shown to induce adenomas and adenocarcinomas in the colons of rats. The present study aimed at providing a better understanding of mechanisms that are responsible for this effect. Three female CD rats were injected i.

Assessment of DNA adducts and the frequency of 6-thioguanine resistant T-lymphocytes in F344 rats fed 2,4-toluenediamine or implanted with a toluenediisocyanate-containing polyester polyurethane foam.

Toluenediamines have been of toxicological concern because of their industrial use as intermediates in polyurethane synthesis and because of the potential of their release from degradation of the Microthane polyesterurethane covering of some breast implants. In this study, we have assessed the extent of DNA damage in rats treated with a carcinogenic toluenediamine isomer, 2,4-toluenediamine (2,4-TDA), under conditions that result in tumor induction, and in rats implanted with Microthane polyesterurethane foam. Time and dose-dependent formation of adducts was observed in DNA from the liver and mammary gland of rats fed 10, 40, 80 and 180 ppm 2,4-TDA for up to 6 weeks.

Relationships of DNA adduct formation, K-ras activating mutations and tumorigenic activities of 6-nitrochrysene and its metabolites in the lungs of CD-1 mice.

6-Nitrochrysene (6-NC), an environmental pollutant and a potent mouse lung carcinogen, is activated by two major metabolic pathways to yield DNA adducts derived from either trans-1,2-dihydro-1,2-dihydroxy-6-aminochrysene (1,2-DHD-6-AC) or N-hydroxy-6-aminochrysene (N-OH-6-AC). While the former pathway has been shown to be the major activation pathway leading to DNA adducts in mice treated with 6-NC, the potential contribution of the minor nitroreduction pathway to tumorigenicity in this system is not clear. To evaluate the roles of these activation pathways and the resulting DNA adducts in mouse lung tumorigenesis, we studied DNA adduct formation, the induction of tumors and tumor K-ras mutational spectra in the lungs of male CD-1 mice treated with 6-NC and its metabolites.

Ethynylestradiol protection against methyl insufficiency in castrated male Wistar/Furth rats fed a methionine-choline-deficient diet.

The interactive effects of dietary methyl insufficiency and the estrogenic compound ethynylestradiol (EE) on the levels of S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) were examined in the liver, lungs and pancreas of rats. In addition, such effects on the hepatic content of 5-methyl-deoxycytidine (5-MC) in nuclear DNA were determined. Castrated male Wistar/Furth rats were fed various levels of EE in either: (i) a complete, amino acid-defined diet (diet 1); (ii) the same diet lacking in choline and methionine and supplemented with 0.