A review of the coordinated research effort on the comparison of test systems for the detection of mutagenic effects, sponsored by the E.E.C.
Under the Environmental Research Programme of the Commission of the European Communities a coordinated comparative test programme was started to assess the mutagenic effects of chemicals in as many different assay systems as possible. A preliminary report is given on the results for 5 compounds selected by the Contact Group "Genetic Effects of Chemicals". 11 laboratories contributed data from tests in their expertise. The compounds were methyl methanesulfonate (MMS), N-nitrosodiethylamine (DEN), mitomycin C (MC), procarbazine (Natulan) and atrazine. The results of testing these 5 compounds in more than 20 test systems are still incomplete but some observations can be made at this time. MMS has been shown to be mutagenic in every system used in this collaborative effort which is not surprising in view of the fact that MMS is a widely used reference mutagen that does not require metabolic activation. Among the indirect mutagens which were tested, MC has been shown to be mutagenic with almost every system which has been applied. DEN which requires microsomal activation gave positive results in most submammalian systems as well as in mammalian cells in culture when the S9 fraction of liver homogenate was added. However, in whole mammals most results were negative. One study suggests that the difference in the results with DEN may be due to the short biological half-life of the mutagenically active metabolite. Procarbazine was negative in the microbial tests but gave a positive response in mammalian cells in culture, in Drosophila and in mammals. Atrazine has only been subjected to a limited amount of testing but the results indicate that plant metabolic activation is required in vitro, and that activation to a mutagenic metabolite also occurs in mammals independent from liver enzymes.
D000818:Animals; D001233:Aspergillus nidulans / Q000235:genetics; D001280:Atrazine / Q000494:pharmacology; D002467:Cell Nucleus / Q000187:drug effects; D002875:Chromosomes / Q000187:drug effects; D004052:Diethylnitrosamine / Q000494:pharmacology; D004331:Drosophila melanogaster / Q000235:genetics; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D005260:Female; D005799:Genes, Dominant; D005808:Genes, Recessive; D005821:Genetic Techniques; D008297:Male; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D051379:Mice; D008937:Mitomycins / Q000494:pharmacology; D009153:Mutagens; D009154:Mutation; D011344:Procarbazine / Q000494:pharmacology; D051381:Rats; D012486:Salmonella typhimurium / Q000235:genetics; D012854:Sister Chromatid Exchange
D008937:Mitomycins; D009153:Mutagens; D011344:Procarbazine; D004052:Diethylnitrosamine; D008741:Methyl Methanesulfonate; D001280:Atrazine