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New mouse somatic cell mutants resistant to cadmium affected in the expression of their metallothionein genes

✍ Scribed by Arvind Chopra; Jacques Thibodeau; You Cheuk Tam; Claude Marengo; Majambu Mbikay; Jean-Paul Thirion


Publisher
John Wiley and Sons
Year
1990
Tongue
English
Weight
916 KB
Volume
142
Category
Article
ISSN
0021-9541

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✦ Synopsis


Fluctuation test5 2 la Luria and Delbruck were performed with mouse LMTK cells, and the result3 indicate that the appearance of variants resistant to cadmium i s due to random spontaneous mutations and not to epigenetic events. The rate of spontaneous mutations leading to cadmium resistance was calculated to be 0.92

x l o p 6 per cell per generation. This rate increased 14-fold on treatment with ethyl methane sulfonate. Several stable mutant cell lines resistant to cadmium were selected and characterized with respect to metallothionein (MT) induction. Based on the copy number of nit+ genes and the levels of MT proteins and mRNA, the mutants could be divided into two classes, A and €3. Although group A mutants have the same number of mtl + and mt2+ genes as wild-type cells, upon induction with cadmium, the amount of MT proteins and mRNA in the mutants are greatly increased over wild-type levels. This observation strongly suggests a mutation that regulates MT gene transcription in these cells. In group B mutants, the mt+ genes are amplified about three-to fourfold, and their M T protein and mRNA basal levels are, as expected, much higher than in the wildtype cells, under uninduced and induced conditions.