Comparison of the Mutational Specificities Exhibited by BPDE in Escherichia Coli and CHO Cells

Abstract

BPDE is presumably the ultimate reactive metabolite of benzo[a]pyrene (B[a]P), a well known carcinogenic environmental pollutant. It has become evident that most chemical carcinogens are active only after metabolism to an ultimate carcinogenic and mutagenic form. These ultimate carcinogens tend to be electron deficient and thus react with nuclephilic sites which are abundant in DNA. It has been established that B[a]P is metabolized by the mixed function oxygenases to a variety of products, including the four enantiomeric forms of BPDE (anti or syn; ( + ) or (−)) (Fahl, 1982). Interestingly, metabolism of B[a]P in mammalian cells produces primarily the (+) anti-BPDE isomer (Yang, et al., 1978). However, not all DNA reactions with these ultimate carcinogens are of equal biological importance. It has been shown at the hprt locus in CHO cells that the respective mutagenic efficiency of BPDE is (+)anti > >(−)anti = (+/−)syn, and remarkably the reverse is seen at the crpt locus in TA100 bacteria (−) anti = (+/−) syn > ( + ) anti (Stevens, et al., 1985). It is also known that the ( + ) anti enantiomer is more than 60 fold more active as a tumor initiator in CD-1 and Sencar mice (Pelling, et al., 1984).