title: Modification of enzyme sulfhydryl groups suppresses UV-induced mutagenesis depending on the nucleotide excision repair system in Escherichia coli B/r WP2.
abstract: S-Methyl methanethiosulfonate (MMTS), which was isolated from cauliflower (Brassica oleracea var. botrytis) homogenate as a potent bio-antimutagen, has been used as an enzyme-sulfhydryl (SH) temporary blocking agent in modification studies of enzyme activities. We examined whether 23 kinds of MMTS-related compounds have a suppressing effect on UV mutagenesis in Escherichia coli B/r WP2. Disulfide derivatives of diphenyl, 2.2'-dipyridine and 4.4'-dipyridine, and N-ethyl maleimide (NEM), which temporarily or tightly block sulfhydryl (SH)-groups, showed similar suppressing effect in E. coli B/r WP2, but not in WP2s hcr- (uvrA-) in the range of nanomolar/plate as MMTS previously did. Cystamine sulfate, methyl methylsulfinylmethyl sulfide and S-methyl-L-cysteinesulfoxide moderately suppressed, and diallyl disulfide and glutathione (oxidized form) weakly suppressed UV mutagenesis in E. coli B/r WP2 in the range of micromolar/plate. MMTS and phorone, a glutathione (GSH)-depleting agent, lowered the intracellular GSH level in E. coli B/r WP2, but phorone did not inhibit UV-induced mutation. These results indicate that the target for SH-modification is enzyme-SHs but not GSH, and that the direct or indirect modification of enzyme-activity by SH-blocking might be involved in the antimutagenesis through a pathway associated with the DNA-excision repair system.
authors.affiliation: Laboratory of Health Science, School of Pharmaceutical Sciences, University of Shizuoka, Japan. nakaty@ys7.u-shizuoka-ken.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Y K
authors.initials: YK
authors.lastname: Nakamura
authors.forename: S
authors.initials: S
authors.lastname: Tashiro
authors.forename: K
authors.initials: K
authors.lastname: Mukai
authors.forename: I
authors.initials: I
authors.lastname: Tomita
mesh_terms: D016587:Antimutagenic Agents / Q000494:pharmacology*; D004260:DNA Repair; D004926:Escherichia coli / Q000235:genetics; D005978:Glutathione / Q000037:antagonists & inhibitors; D007659:Ketones / Q000494:pharmacology; D008698:Mesylates / Q000494:pharmacology*; D016296:Mutagenesis / Q000187:drug effects*; D013439:Sulfhydryl Reagents / Q000494:pharmacology*; D014466:Ultraviolet Rays
chemical_list: D016587:Antimutagenic Agents; D007659:Ketones; D008698:Mesylates; D013439:Sulfhydryl Reagents; C074502:methanethiosulfonate; C018637:phorone; D005978:Glutathione