Possible enhancing effects of atrazine and nonylphenol on 7,12-dimethylbenz[a]anthracene-induced mammary tumor development in human c-Ha-ras proto-oncogene transgenic rats
| Autor: | Eiji Matsuda, Hiroyuki Tsuda, Chuel Kyu Kim, Katsumi Fukamachi, Tomomi Yamasaki, Yoichiro Matsuoka, Nobuo Takasuka, Beom Seok Han |
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| Rok vydání: | 2004 |
| Předmět: |
Male
Cancer Research medicine.medical_specialty 9 10-Dimethyl-1 2-benzanthracene Administration Oral DMBA Endocrine System Mammary Neoplasms Animal Biology Proto-Oncogene Mas Risk Assessment Animals Genetically Modified chemistry.chemical_compound Phenols Internal medicine medicine Animals Humans Endocrine system Bioassay Drug Interactions Genetic Predisposition to Disease Atrazine Carcinogen Mammary tumor Dose-Response Relationship Drug Herbicides 7 12-Dimethylbenz[a]anthracene General Medicine Animal Feed Rats Nonylphenol Disease Models Animal Genes ras Endocrinology Oncology chemistry Carcinogens Biological Assay Female |
| Zdroj: | Cancer Science. 95:404-410 |
| ISSN: | 1349-7006 1347-9032 |
| DOI: | 10.1111/j.1349-7006.2004.tb03223.x |
| Popis: | Our transgenic (Tg) strain carrying copies of the human c-Ha-ras proto-oncogene is highly susceptible to 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary carcinogenesis, possibly due to activation of the transgene, and can be used in medium-term bioassay models to test for modifying effects of estrogenic environmental compounds on tumor development. The present study was conducted to assess the influence of dietary feeding of the endocrine disruptors atrazine and nonylphenol on DMBA-induced carcinogenesis in c-Ha-ras Tg rats. Animals of both sexes were given a single oral dose of DMBA (25 mg/kg body weight) at 50 days of age and thereafter received soybean-free diet containing 5, 50 or 500 ppm atrazine, or 10, 25, 100 or 250 ppm nonylphenol. In female Tg rats, atrazine at a dose of 5 ppm increased the incidences of mammary adenomas and adenocarcinomas (P < 0.01 and P < 0.05), while 50 ppm increased the adenocarcinoma incidence (P < 0.05). In males, skin tumor development, in contrast, was significantly decreased at the highest dose. Nonylphenol at 10 ppm increased adenocarcinoma and total mammary tumor multiplicity in female Tg rats (P < 0.05), but there was no dose dependence, a significant quadratic dose-response trend rather being observed (P < 0.05). In vitro, atrazine did not cause proliferation of MCF-7 cells at any of a range of doses tested. These results suggest that endocrine disruptors may enhance mammary carcinogenesis, but only in a certain limited dose range under the present experimental conditions. The doses applied, moreover, were all extremely high compared to the possible environmental human exposure levels. |
| Databáze: | OpenAIRE |
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