Lethal and mutagenic actions of N-methyl-N'-nitro-N-nitrosoguanidine potentiated by oxidized glutathione, a seemingly harmless substance in the cellular environment.
نویسندگان
چکیده
Both the lethal and the mutagenic actions of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) on cells of Streptococcus pneumoniae were greatly potentiated by a component of yeast extract added to the cellular environment. This component was found to be an oxidation product of glutathione, glutathione disulfide (GSSG). At low concentrations in the medium, both GSSG and glutathione potentiated MNNG action, but at high concentrations, glutathione (and other sulfhydryl compounds) abolished the effect. Point mutations in a cellular gene conferred resistance to the potentiating effect, and they blocked uptake of either GSSG or glutathione into the cells as well. This gene apparently encodes a component of the system for glutathione transport in S. pneumoniae. The mechanism by which GSSG, an apparently innocuous substance in the environment, renders low levels of MNNG genotoxic and cytotoxic thus depends on its transport into the cell, where it is reduced by glutathione reductase and then activates intracellular MNNG. Also, it was observed that mutants of S. pneumoniae defective in DNA mismatch repair are more resistant to MNNG than are wild-type cells by a factor of 2.5.
منابع مشابه
Anti-mutagenic and Anti-oxidant Potencies of Cetraria Aculeata (Schreb.) Fr., Cladonia Chlorophaea (Flörke ex Sommerf.) Spreng. and Cetrelia Olivetorum (Nyl.) W.L. Culb. & C.F. Culb.)
In this study, the mutagenic and anti-mutagenic effects of methanol extract of three lichen species (Cetraria aculeata, Cladonia chlorophae and Certalia olivetorum) were investigated by using E.coli-WP2, Ames-Salmonella (TA1535 and TA1537) and sister chromatid exchange (SCE) test systems. The results obtained from bacterial test systems demonstrated that methanol extracts of three lichen specie...
متن کاملAnti-mutagenic and Anti-oxidant Potencies of Cetraria Aculeata (Schreb.) Fr., Cladonia Chlorophaea (Flörke ex Sommerf.) Spreng. and Cetrelia Olivetorum (Nyl.) W.L. Culb. & C.F. Culb.)
In this study, the mutagenic and anti-mutagenic effects of methanol extract of three lichen species (Cetraria aculeata, Cladonia chlorophae and Certalia olivetorum) were investigated by using E.coli-WP2, Ames-Salmonella (TA1535 and TA1537) and sister chromatid exchange (SCE) test systems. The results obtained from bacterial test systems demonstrated that methanol extracts of three lichen specie...
متن کاملSensitivity of human cell strains having different abilities to repair O6-methylguanine in DNA to inactivation by alkylating agents including chloroethylnitrosoureas.
In order to investigate the mechanisms of cellular damage by alkylating agents, human fibroblasts and tumor cell strains having different sensitivities to killing by N-methyl-N'-nitro-N-nitrosoguanidine [and different abilities to repair O6-methylguanine ( O6mGua ) in their DNA] were treated with other alkylating agents. Methyl methanesulfonate, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), 1-(2...
متن کاملMutagenic action of N-methyl-N'-nitro-N-nitrosoguanidine on Gaffkya tibisci at alkaline pH.
Good yields of mutants were obtained by incubating cells of Gaffkya tibisci with N-methyl-N'-nitro-N-nitrosoguanidine in alkaline buffer. Nearly 50% of the survivors were auxotrophic mutants under the conditions described.
متن کاملPostreplication repair and the susceptibility of Chinese hamster cells to cytotoxic and mutagenic effects of alkylating agents.
A cell variant (VR-43) resistant to the cytotoxic effect of N-methyl-N'-nitro-N-nitrosoguanidine and N-methyl-N'-nitro-N-nitrosourea was isolated from Chinese hamster V79 cells for use in studies of the relationship among cell survival, mutagenesis, and DNA repair by alkylating agents. Resistance to ouabain or 6-thioguanine was used as the genetic marker. After treatment with N-methyl-N'-nitro-...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Journal of bacteriology
دوره 177 13 شماره
صفحات -
تاریخ انتشار 1995