Mechanism of phage phiX174 DNA inactivation by benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide.

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RESUMO

A previous report from this laboratory has shown that certain derivatives of polycyclic aromatic hydrocarbons bind to phiX174 DNA and render it noninfectious. The present work describes the relationship between the extent of phiX174 DNA binding by (+/-)-anti-benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide and the effect on infectivity. The results suggest that one molecule of bound diolepoxide is sufficient to inhibit the replication of a single molecule of phiX174 DNA. DNA synthesis studies, in vitro, indicate that when phiX DNA bound by benzo[a]pyrene groups serves as template the rate of DNA polymerization is reduced and less product is formed. In addition, the propagation of synthetic DNA strands is blocked so that incomplete complementary chains are assembled. The relationship of these findings to the mutagenic and carcinogenic process associated with the action of benzo[a]pyrene-diolepoxide is discussed.

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