Prenatal 3,3',4,4',5-pentachlorobiphenyl exposure modulates induction of rat hepatic CYP 1A1, 1B1, and AhR by 7,12-dimethylbenz[a]anthracene
- Department of Toxicologic Pathology, Azabu University School of Veterinary Medicine, 1-17-71 Fuchinobe, Kanagawa 229-8501 (Japan)
- Department of Pathology, Jikei University School of Medicine, Tokyo 105-8461 (Japan)
- Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo 181-8611 (Japan)
- Department of Biochemistry, Azabu University School of Veterinary Medicine, Kanagawa 229-8501 (Japan)
- Department of Pathology, Kyorin University School of Medicine, Tokyo 181-8611 (Japan)
We previously reported the finding that prenatal exposure to a relatively low dose of PCB126 increases the rate of DMBA-induced rat mammary carcinoma, while a high dose decreased it. One of the most important factors determining the sensitivity to mammary carcinogenesis is the metabolic stage at administration of the carcinogenic agent. DMBA is a procarcinogen that recruits the host metabolism to yield its ultimate carcinogenic form, and CYP1A1 and CYP1B1 (CYP1) conduct this metabolism. We investigated the hepatic expression of CYP1 and AhR following oral administration of DMBA (100 mg/kg b.w.) (i.g.) to 50-day-old female Sprague-Dawley rats whose dams had been treated (i.g.) with 2.5 ng, 250 ng, 7.5 {mu}g of PCB126/kg or the vehicle on days 13 to 19 post-conception. Real-time quantitative RT-PCR analysis revealed that the prenatal exposure to a relatively low dose of PCB126 (the 250 ng group) prolonged the higher expression of CYP1A1, CYP1B1, and AhR mRNA, while prenatal exposure to a high dose of PCB126 (the 7.5 {mu}g group) prolonged the higher expression of CYP1A1 and AhR mRNA. Western blotting and immunohistochemical analyses were consistent with mRNAs changes. Because DMBA oxidation produces a highly mutagenic metabolite and is finally catalyzed by CYP1B1, a relatively low PCB126 dose might produce the biological character to potentially increase the risk of DMBA-induced mammary carcinoma.
- OSTI ID:
- 20783419
- Journal Information:
- Toxicology and Applied Pharmacology, Vol. 210, Issue 3; Other Information: DOI: 10.1016/j.taap.2005.04.022; PII: S0041-008X(05)00211-5; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0041-008X
- Country of Publication:
- United States
- Language:
- English
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