Chronic, topical administration of 4-aminobiphenyl induces tissue-specific DNA adducts in mice

Toxicology and Applied Pharmacology
P M UnderwoodG Talaska

Abstract

While current human exposure to 4-aminobiphenyl (4-ABP) is mainly through inhalation, historically, occupational exposure occurred most often through the skin. 4-ABP targets the urinary bladder in humans, dogs, and rats and the liver and urinary bladder in mice. This study examines the time course of DNA adduct levels in mouse target tissues, liver and urinary bladder, and nontarget tissues, lung and skin, after repeated dermal exposure to subcarcinogenic doses of 4-ABP. It was found that, in female mice dermally treated with 50 nmol of 4-ABP twice weekly for 21 weeks, DNA adduct levels measured by 32P-postlabeling increased over time in target and nontarget tissues, but the greatest rate of accumulation occurred in urinary bladder. At 21 weeks liver, urinary bladder, and skin reached their highest median adduct levels of 55, 82, and 58, respectively. Median adduct levels in lung reached a maximum of 3.2 at 3 weeks of exposure. An adduct which had similar chromatographic properties to a standard previously identified as N-(deoxyguanosin-8-yl)-4-aminobiphenyl was the primary adduct detected in all tissues. There were significant correlations in adduct levels between liver and urinary bladder and liver and skin, but not between s...Continue Reading

References

Jun 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·G TalaskaF F Kadlubar
Jul 1, 1985·European Journal of Cancer & Clinical Oncology·G J SchiefersteinG T Burger
Jul 1, 1983·Bulletin of Environmental Contamination and Toxicology·P V Shah, F E Guthrie
Feb 1, 1994·Clinical Pharmacokinetics·D R Krishna, U Klotz
May 1, 1994·Carcinogenesis·W B MelchiorF A Beland
Jul 23, 1996·Proceedings of the National Academy of Sciences of the United States of America·G TalaskaD Warshawsky

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Citations

Nov 9, 2011·Journal of Occupational and Environmental Hygiene·Kathy LaDowGlenn Talaska
Aug 21, 2003·Journal of the National Cancer Institute·Yutaka TsuneokaDaniel W Nebert
May 29, 2002·Toxicology and Applied Pharmacology·Howard G ShertzerDaniel W Nebert

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