Mutagenicity of methyl methanesulfonate (MMS) in vivo at the Dlb-1 native locus and a lacI transgene.
Methyl methanesulfonate (MMS) is an extraordinarily poor mutagen compared to ethylnitrosourea (ENU) or even X-rays. In lung fibroblasts in vivo, MMS has been shown to induce many micronuclei but few, if any, mutations at the hpt locus. We wondered if the lack of mutations might be due to the lack of division and DNA synthesis in fibroblasts in vivo, which would permit substantial time for differential repair of DNA lesions. This idea was tested in the small intestine, a tissue in which the cells are actively dividing. Two loci were examined: a native locus (Dlb-1) which determines the presence or absence of a lectin binding site on the surface of the epithelial cells, and a lacl transgene which controls beta-galactosidase synthesis. Locl mutations were detected after in vitro packaging of DNA isolated from the intestinal epithelium into lambda phage and expression in suitable bacteria. Although the epithelial cells are proliferating, acute treatments produced no significant increase in mutations at either locus. Subacute treatments produced low but significant increases in mutation frequency at both loci. The results confirm that MMS is a far more potent clastogen than it is a mutagen and should be regarded as a super-clastogen in the same manner as ENU is a super-mutagen. The carcinogenicity of MMS is probably the result of its potent clastogenicity rather than its weak activity as a point mutagen.
Tao
K S
KS
Department of Biology, York University, Toronto, Canada.
Urlando
C
C
Heddle
J A
JA
D000818:Animals; D002863:Chromogenic Compounds; D005260:Female; D005697:Galactosides; D007211:Indoles; D008297:Male; D008741:Methyl Methanesulfonate / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009152:Mutagenicity Tests; D009154:Mutation; D011975:Receptors, Mitogen / Q000235:genetics
D002863:Chromogenic Compounds; C027654:Dolichos biflorus lectin receptor; D005697:Galactosides; D007211:Indoles; D011975:Receptors, Mitogen; D008741:Methyl Methanesulfonate; C044888:5-bromo-4-chloro-3-indolyl beta-galactoside