Cytosine attack by free radicals arising from bromotrichloromethane in the presence of benzoyl peroxide catalyst: a mass spectrometric study.

We and others previously reported that CCl4 reactive metabolites are able to covalently bind to liver DNA either in vivo or in vitro. However, no demonstration of the structure of resulting adducts is available in literature. That information would be of relevance, for CCl4 exhibits null or contradictory mutagenic properties and is currently considered a non-genotoxic carcinogen. In the present study we report the nature of the reaction products formed when the putative CCl4 metabolites, .CCl3 and CCl3O2. attack cytosine in a purely chemical system where they were generated from CCl3Br in a benzoyl peroxide catalyzed reaction. Reaction products formed and identified were a) under nitrogen (.CCl3 present)--5-bromo cytosine and cytosine-5-carboxylic acid; b) under air (CCl3O2. present)--5-bromo cytosine, 5-chloro cytosine, 5-hydroxy cytosine, 6-hydroxy cytosine (tentative), chloro hydroxy uracil, 5,6-dihydroxy uracil, and chloro trichloromethyl cytosine. Results from present experiments suggest that if these reaction products were also produced in vivo during either CCl4 or CCl3Br poisoning and they were not repaired in due time prior to replication, they would lead to mutagenic events. Studies directed to obtain evidence for their in vivo formation are in course in our laboratory.