Genotoxicity studies of benz[l]aceanthrylene |
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| Authors: | A D Kligerman M M Moore G L Erexson K H Brock C L Doerr J W Allen S Nesnow |
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| Affiliation: | 1. Environmental Health Research and Testing, Inc., P.O. Box 12199, Research Triangle Park, NC 27709 U.S.A.;2. Genetic Toxicology Division, Health Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 U.S.A.;1. First People''s Hospital of Shangqiu, Henan Province, Shangqiu, 476100, China;2. Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Yanbian University, College of Pharmacy, Yanji, Jilin, 133002, China;3. Shangqiu Municipal Hospital, Henan Province, Shangqiu, 476100, China;4. Rega Institute for Medical Research, Medicinal Chemistry, KU Leuven, Herestraat 49-Box 1041, 3000, Leuven, Belgium;1. Department of Genetic Toxicology, Charles River Laboratories, Montreal, ULC, Canada;2. Boone, North Carolina, USA;1. Faculty of Health Sciences, Federal University of Grande Dourados, Dourados, MS, Brazil;2. Faculty of Biological and Environmental Sciences, Federal University of Grande Dourados, Dourados, MS, Brazil;3. Faculty of Exact Sciences and Technology, Federal University of Grande Dourados, Dourados, MS, Brazil;1. Rita Schoeny, LLC, Washington, DC 20002, United States;2. Leadscope, Inc., 1393 Dublin Road, Columbus, OH 43215, United States;3. U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, United States;4. U.S. Food and Drug Administration, Center for Devices and Radiological Health, Silver Spring, MD 20993, United States;5. Tsukuba Drug Safety, Eisai Co., Ltd., Tsukuba, Ibaraki, 300-2635, Japan;6. U.S. Food and Drug Administration, Center for Food Safety and Applied Nutrition, College Park, MD 20740 United States;7. Lhasa Limited, 2 Canal Wharf, Leeds, LS11 5PS, United Kingdom;8. Errol Zeiger Consulting, 800 Indian Springs Road, Chapel Hill, NC 27514, United States;9. Merck & Co., West Point, PA 19486, United States;10. GSK R&D, Hertfordshire, United Kingdom;11. CMIC Pharma Science Co., Ltd., Hokuto, Yamanashi, Japan;12. Boehringer Ingelheim Pharma GmbH & Co., KG, Birkendorfer Strasse 65, 88397 Biberach an der Riss, Germany;13. Ramboll US Corporation Little Rock, AR 72223, United States;14. Merck KGaA, Frankfurter Straβe 250, Darmstadt, 64293, Germany;15. Charles River Laboratories - Skokie, LLC, 8025 Lamon Ave., Skokie, IL 60077, United States;p. Division of Genetics and Mutagenesis, National Institute of Health Sciences, Kawasaki, Kanagawa, 210-9501, Japan;q. Non-Clinical Safety Janssen R&D, a Division of Janssen Pharmaceutica N.V., Beerse, Belgium;1. US Food and Drug Administration, Center for Food Safety and Applied Nutrition, College Park, MD, 20740, USA;2. Errol Zeiger Consulting, Chapel Hill, NC, 27514, USA;3. Merck & Co. Inc., West Point, PA, USA;4. Tsukuba Drug Safety, Eisai Co., Ltd., Tsukuba, Ibaraki, 300-2635, Japan;5. Non-Clinical Safety, Janssen Research & Development, a Division of Janssen Pharmaceutica N.V., Beerse, Belgium;6. CMIC Pharma Science Co., Ltd., Hokuto, Yamanashi, Japan;7. Ramboll US Corporation, Little Rock, AR, 72201, USA;8. Division of Genetics and Mutagenesis, National Institute of Health Sciences, Kawasaki, Kanagawa, 210-9501, Japan |
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| Abstract: | The genotoxicity of the cyclopenta-fused polycyclic aromatic hydrocarbon, benz[l]aceanthrylene (B[l]A), was evaluated in vitro using the L5178Y/TK+/- mouse lymphoma assay and in vivo using the mouse peripheral blood lymphocyte (PBL) culture system. The mutagenicity and sister chromatid exchange (SCE) inducing potential of B[l]A was then compared to that of benzo[a]pyrene (B[a]P). B[l]A appeared to be slightly less mutagenic than B[a]P at the TK locus, and each compound produced both small and large colony mutants indicating that they are clastogenic as well as mutagenic. Gross chromosome aberration analysis of treated L5178Y/TK+/- mouse lymphoma cells confirmed the clastogenicity of B[l]A in vitro. In the mouse PBL system, after administration by gavage, B[l]A was more cytotoxic and produced a sharper elevation in SCE frequency than B[a]P. |
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