The mutagenic potency of 4 agents at the thymidine kinase locus in mouse lymphoma L5178Y cells in vitro: effects of exposure time.
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 micrograms/ml using short exposure times, whereas the compound was active at concentrations as low as 0.1 microgram/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 micrograms/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 micrograms/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.
D000818:Animals; D001560:Benzidines / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005020:Ethyl Methanesulfonate / Q000633:toxicity; D008223:Lymphoma / Q000201:enzymology / Q000235:genetics; D051379:Mice; D009152:Mutagenicity Tests; D009154:Mutation / Q000187:drug effects*; D011721:Pyrenes / Q000633:toxicity; D011929:Razoxane / Q000633:toxicity; D013937:Thymidine Kinase / Q000235:genetics*
D001560:Benzidines; D011721:Pyrenes; C029876:benzidine; C033310:1,8-dinitropyrene; D011929:Razoxane; D005020:Ethyl Methanesulfonate; D013937:Thymidine Kinase