DNA and RNA Adducts Formed in Hamster Embryo Cell Cultures Exposed to Benzo [a] pyrene

The time course of covalent binding of [14C] benzo [a] pyrene (BP) to RNA and DNA in hamster embryo cell cultures and types of nucleoside adducts have been investigated. Binding to RNA proceeded rapidly and followed a linear time course for at least 48 h. In contrast, the extent of binding to DNA reached a plateau after approximately 18 h of incubation with [14C] BP. Fluorescence spectroscopy of the modified nucleic acids and high-pressure liquid chromatography of the nucleoside adducts provided evidence that benzo [a] pyrene-7,8-dihydrodiol 9,10-oxide (BPDE) is the major metabolite of BP responsible for covalent modification of hamster embryo cellular nucleic acids. Both BPDE I and II isomers are synthesized and participate in modification of the host cell's RNA and DNA. Although guanine is the major BPDE target during in vivo modification of RNA and DNA, there is a low but detectable modification of adenine and cytosine bases. The relative contributions of the various isomers of BPDE to in vivo nucleic acid modification vary between DNA and RNA. The types of RNA adducts do not depend on the length of time of exposure to BP. In contrast, the relative amounts of the multiple types of DNA adducts changed with time, suggesting that they underwent differential rates of excision. A greater heterogeneity of the DNA adducts in primary hamster embryo cell cultures was observed than in previous studies with human and bovine bronchial explants exposed to BP. Possible differences in DNA-BPDE adducts among species and cell types are discussed.