Specific DNA adducts induced by some mono-substitued epoxides in vitro andin vivo

Alkyl epoxides are important intermediates in the chemical industry. They a re also formed in vivo during the detoxification of alkenes. Alkyl epoxides have shown genotoxicity in many toxicology assays which has been associate d with their covalent binding to DNA. Here aspects of the formation and pro perties of DNA adducts, induced by some industrially important alkenes and mono-substituted epoxides are discussed. These include propylene oxide, epi chlorohydrin, allyl glycidyl ether and the epoxy metabolites of styrene and butadiene. The major DNA adducts formed by epoxides are 7-substituted guan ines, 1- and 3-substituted adenines and 3-substituted cytosines. In additio n, styrene oxide and butadiene monoepoxide are able to modify exocyclic sit es in the DNA bases, the sites bring in the case of styrene oxide N-2- and O-6-positions of guanine, N-6-adenine as well as N-4-and O-2-cytosine. In v ivo the main adduct is the 7-substituted guanines. The 1-substituted adenin es have also shown marked levels, and these adducts should also be targets in biomonitoring of human exposures. Due to its low mutagenicity, 7-substit uted guanines are considered as a surrogate marker for other mutagenic lesi ons, e.g. those of 1-adenine or 3-uracil adducts. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.