P-postlabeling analysis of DNA adducts formed in vitro and in rat skin by methylenediphenyl-4,4'-diisocyanate (MDI) |
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Authors: | Esther H Vock Sergio Cantoreggi Ramesh C Gupta Werner K Lutz |
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Institution: | 1. Institute of Toxicology, Swiss Federal Institute of Technology and University of Zürich, CH-8603 Schwerzenbach, Switzerland;2. Preventive Medicine and Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40506, USA |
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Abstract: | The 32P-postlabeling method was adapted for the detection of DNA adducts formed by methylenediphenyl-4,4'-diisocyanate (MDI). Incubation of the 3'-phosphates of the deoxyribosides of cytosine (C), adenine (A), guanine (G) and thymine (T) with MDI in Tris buffer resulted in the formation of 5, 7, 8, and 2 reaction products, respectively. Incubation of DNA with MDI resulted in detectable levels of 5, 2, and 1 adducts attributable to C, A, and G. Analysis of DNA isolated from the epidermis of rats treated dermally with 9 mg MDI showed an adduct pattern similar to the one seen in the in vitro DNA incubation. A total adduct level of 7 per 108 nucleotides was measured, the limit of detection was 2 adducts per 1010 nucleotides. The data indicate that a minute fraction of MDI can reach DNA in vivo in a chemically reactive form. In comparison with the genotoxic skin carcinogen 7,12-dimethylbenza]anthracene on the other hand, the DNA-binding potency of MDI was more than 1000-fold lower. |
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Keywords: | Isocyanate Genotoxicity Skin |
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