The role of glutathione in the bacterial mutagenicity of vapour phase dichloromethane.
Dichloromethane (DCM) vapour by inhalation is carcinogenic to rodents and is an in vivo rodent cell clastogen and a bacterial mutagen. It has been suggested that the bacterial mutagenicity of DCM is mediated by glutathione (GSH) conjugation. The involvement of endogenous and exogenous GSH in the conversion of DCM to a bacterial mutagen has been studied in a vapour phase protocol using wild-type and GSH-deficient (NG54; gsh) Salmonella typhimurium TA100 strains in the presence and absence of various rat liver fractions. The effect of the duration of exposure was also investigated in these Salmonella strains and in E. coli WP2 uvrA pKM101. Dose- and time-related increases in revertants occurred with all metabolic activation systems used (without exogenous metabolic activation; with Aroclor-induced rat liver S9, microsomes, or cytosol fractions), with minor quantitative differences among the 3 strains. Mutagenicity was marginally highest in the presence of cytosol at the highest DCM concentrations. Strain NG54 gsh, which contains approximately 25% of the TA100 level of GSH/microgram protein, was slightly less responsive to DCM-induced mutagenicity than TA100. Addition of 0.33 mumoles/plate of GSH had little effect on the mutagenic responses of TA100 or NG54 in the presence or absence of S9. In these 2 strains, exogenous S9 produced small increases in mutagenicity at the highest concentrations of DCM (2 and 4% v/v). These results suggest that if an interaction between DCM and GSH is required for the activation of DCM to a bacterial mutagen, it occurs at low levels of endogenous GSH and is not significantly affected by GSH supplementation.
Dillon
D
D
Inveresk Research International Ltd., Tranent, Scotland.
Edwards
I
I
Combes
R
R
McConville
M
M
Zeiger
E
E
D000818:Animals; D001711:Biotransformation; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008752:Methylene Chloride / Q000494:pharmacology*; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests; D009153:Mutagens / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000378:metabolism
D009153:Mutagens; D008752:Methylene Chloride; D005978:Glutathione