Development of a System to Study Gene Activation in Mammalian Cells Treated with BIS (2-Chloroethyl) Sulfide.

摘要

We have shown that treatment of S49 mouse lymphoma cells with sulfur mustard (SM) results in about a 150-fold increase in the frequency of cadmium-resistant (Cdr) variants compared to untreated controls (1). We have examined 18 of these Cdr variants in detail as well as 5 spontaneous variants, and we find that virtually all of them make metallothionein I (MT-I), metallothionein II (MT-II), or both. The spontaneous Cdr variants make only MT-II, while the Cdr variants from sulfur-mustard-treated cells often synthesize both RNAs (Ribonucleic acids). In a series of genomic blotting experiments (southern blots), we found that most of these MT+ lines showed no major amplifications, gene rearrangements, or deletions, thus ruling out such changes as the major cause for the activation of these genes. Analysis of DNA (Deoxynbonucleic acids) methylation patterns by Hpa II (endonuclease) digestion followed by genomic blotting revealed a complex pattern of demethylation in MT+ variants, but no consistent pattern. RA V, Cultured mouse cells, Gene amplification, Alkylating agents, Nucleic acids, Enzymes. (jg)