The mutagenic potency of 4 agents at the thymidine kinase locus in mouse lymphoma L5178Y cells in vitro: Effects of exposure time

Abstract

Mutagenic potency at the thymidine kinase (TK) locus in mouse lymphoma L5178Y cells (expressed as induced trifluorothymidine (TFT)-resistant mutants/total dose) was assessed for 4 agents (ethyl methanesulphonate (EMS), benzidine, 1,8-dinitropyrene (1,8-DNP) and ICRF 159) using short (3–4 h) and long (21–24 h) exposure times. The mutagenic potency of EMS was found to be essentially independent of concentration and exposure time when tested over a cytotoxic range consistent with routine testing procedures. Similar results were obtained with benzidine but for both 1,8-DNP and ICRF 159 mutagenic potency was found to be highly dependent on the concentration and exposure time. 1,8-DNP failed to induce any significant increases in mutant frequency when tested at concentrations up to 5 μg/ml using short exposure times, whereas the compound was active at concentrations as low as 0.1 μg/ml when the exposure period was extended to 21 h. Under the latter conditions, however, the molar potency of 1,8-DNP was found to be inversely related to concentration over a range extending from 0.1 to 5 μg/ml. ICRF 159 induced increases in the frequency of TFT-resistant mutants using short or long exposure times. When a short exposure time was used, however, the mutagenic potency of the antitumour agent decreased with increasing concentration between 1 and 500 μg/ml. Although possible explanations can be offered to account for these observations the results illustrate potential problems which may arise in this system when comparing mutagenic potency values for a range of compounds with a view to assessing relative risk.