Genotoxicity of 1,3- and 1,6-dinitropyrene: induction of micronuclei in a panel of mammalian test cell lines |
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| Institution: | 1. Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40292, USA;2. Department of Environmental Health Science, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, China;3. Biostatisitcs and Bioinformatics Shared Facility, JGB Cancer Center and Department of Bioinformatics and Biostatistics, University of Louisville, Louisville, KY 40292, USA;1. Department of Neurosurgery, The Fourth Affiliated Hospital, Harbin Medical University, Harbin, China;2. Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China;3. Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China;4. Department of Clinical Laboratory, Beijing Shijiantan Hospital, Capital Medical University, Beijing, China;5. Department of General Surgery, Shanghai Chang Zheng Hospital, Second Military Medical University, Shanghai, China;1. Department of Infectious Diseases and;2. Department of Gastroenterology and Hepatology, The First Hospital of Lanzhou University, The First Medical College of Lanzhou University, Lanzhou University, Lanzhou, Gansu, China;3. Department of General Surgery, Lanzhou University Second Hospital, The Second Medical College of Lanzhou University, Lanzhou University, Lanzhou, Gansu, China |
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| Abstract: | 1,3-Dinitropyrene (1,3-DNP) and 1,6-dinitropyrene (1,6-DNP) were assessed for their potential to increase the frequencies of micronuclei in a panel of test cell lines consisting of H4IIEC3/G, 5L, 5L/r-1,3-DNP1, 208F, V79, V79/r-1,6-DNP1, HepG2 and BWI-J cells, which have been partially characterized for their expression of xenobiotic metabolising enzymes. The micronuclei were analyzed for the presence or absence of kinetochores indicating the occurrence of aneuploidy or chromosome breakage, respectively. 1,3-DNP caused a substantial increase in the frequency of micronuclei only in V79 cells. 1,6-DNP was strongly genotoxic in lines H4IIEC3/G?, 208F, V79 and, to a minor degree, in 5L/r-1,3-DNP1. It caused the formation of kinetochore-positive as well as kinetochore-negative micronuclei in V79 cells but only of kinetochore-negative micronuclei in H4IIEC3/G? and 208F cells. 1,6-DNP-induced formation of micronuclei was paralleled by the appearance of multinucleated cells. Treatment of V79 cells with 1,3-DNP resulted in the same types of damage as treatment with 1,6-DNP, although considerably higher concentrations were required.The results show that 1,6-DNP can be highly genotoxic in mammalian cells, whereas, at least in the panel of test cell lines used, 1,3-DNP possesses only a low genotoxic activity. 1,3-DNP appears to be activated to genotoxic products in V79 cells by the same pathway(s) as 1,6-DNP. |
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