Reversion of 6-thioguanine resistant Chinese hamster cell lines: agent specificity and evidence for the repair of promutagenic lesions

Abstract

The kinetics and mutagen specificity of reversion of an HGPRT-TG^R line of Chinese hamster cells have been examined in detail by measuring the frequency of HAT^R colonies. Alkylating agents which produce relatively high levels of O-atom reaction were effective in inducing reversion. MMS, DMS and u.v. were less efficient, and aflatoxin B₁, acridine orange and N-acetoxy-AAF were completely ineffective. For agents which were effective, the relationship between HAT^R colony frequency and dose of mutagen was linear at early expression times (6 h). HAT^R colony frequency fell subsequently at all doses and the rate and extent of the fall was inversely related to dose. These observations suggest repair of a pro-mutagenic DNA lesion. Other TG^R mutants isolated from the same wild-type cell line under different selective conditions were also tested for revertibility after exposure to the same mutagens. The majority did not revert, this suggests that they carry deletions within the structural gene for HGPRT. The infrequent revertible lines all arose spontaneously and our evidence suggests that they carry nonsense mutations.