The mammalian spot test and its use for testing of mutagenic and carcinogenic potential: experience with the pesticide chlordimeform, its principal metabolites and the drug lisuride hydrogen maleate.
The mammalian spot test has recently been demonstrated to be a promising method for the detection of somatic mutations induced by chemicals and is at present under validation as an in vivo screening test for carcinogenic potential. The pesticide chlordimeform, its principal metabolites N-formyl-4-chloro-o-toluidine and 4-chloro-o-toluidine, and the drug lisuride hydrogen maleate, as well as the known mutagens ethyl methanesulfonate (EMS) and N-ethyl-N-nitrosourea (ENU) were tested in the mammalian spot test. Female C57BL/6J mice were mated to T-stock males and treated by gavage with maximal tolerated doses of the test compounds, or by intraperitoneal injection with EMS and ENU at days 8, 9 and 10 of pregnancy. Mutation induction was monitored post-natally by checking the fur of the offspring for color spots that result from expression of a recessive gene involved in coat-color determination. Of the environmental chemicals tested, only 4-chloro-o-toluidine was mutagenic in the spot test. This positive result was in agreement with in vitro experiments and its carcinogenic potential in the mouse. However, the mouse carcinogens chlordimeform and N-formyl-4-chloro-o-toluidine were negative, as was the non-carcinogen lisuride hydrogen maleate. N-Formyl-4-chloro-o-toluidine and lisuride hydrogen maleate have been reported to be weakly positive in the Ames test. The positive controls EMS and ENU showed a clear mutagenic response.
D000578:Amidines / Q000633:toxicity*; D000818:Animals; D001711:Biotransformation; D002273:Carcinogens; D002742:Chlorphenamidine / Q000633:toxicity*; D004353:Drug Evaluation, Preclinical; D004873:Ergolines / Q000633:toxicity*; D005038:Ethylnitrosourea / Q000633:toxicity; D005260:Female; D005799:Genes, Dominant / Q000187:drug effects; D005804:Genes, Lethal / Q000187:drug effects; D005838:Genotype; D008090:Lisuride / Q000633:toxicity*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009152:Mutagenicity Tests; D009153:Mutagens; D009154:Mutation; D011247:Pregnancy
D000578:Amidines; D002273:Carcinogens; D004873:Ergolines; D009153:Mutagens; D008090:Lisuride; D002742:Chlorphenamidine; D005038:Ethylnitrosourea