In vivo covalent binding of chemicals to DNA as a short-term test for carcinogenicity

The determination of a covalent binding of radioactive chemicals to DNA in intact mammalian organisms is proposed as a short-term test for carcinogenicity. The effectiveness of covalent binding to rat liver DNA correlates well with the hepatocarcinogenicity known from long-term bioassays. The binding indices range over more than five orders of magnitude between the strongest hepatocarcinogen aflatoxin B1 and the limit of detection of a binding with 100 muCi 14C-labelled chemical. The order of magnitude of binding is therefore a surprisingly good quantitative measure for carcinogenicity. The pattern of DNA binding sites is important especially for small alkylating agents where the determination of total binding might indicate a higher carcinogenic potency than is actually observed.