The role of formaldehyde and S-chloromethylglutathione in the bacterial mutagenicity of methylene chloride
Graves, RJ; Callander, RD; Green, T
HERO ID
626445
Reference Type
Journal Article
Year
1994
Language
English
PMID
| HERO ID | 626445 |
|---|---|
| In Press | No |
| Year | 1994 |
| Title | The role of formaldehyde and S-chloromethylglutathione in the bacterial mutagenicity of methylene chloride |
| Authors | Graves, RJ; Callander, RD; Green, T |
| Journal | Mutation Research |
| Volume | 320 |
| Issue | 3 |
| Page Numbers | 235-243 |
| Abstract | Methylene chloride was less mutagenic in Salmonella typhimurium TA100/NG-11 (glutathione-deficient) compared to TA100, indicating that glutathione is involved in the activation of methylene chloride to a mutagen in bacteria. In rodents, the pathway of methylene chloride metabolism utilizing glutathione produces formaldehyde via a postulated S-chloromethylglutathione conjugate (GSCH2Cl). Formaldehyde is known to cause DNA-protein cross-links, and GSCH2Cl may act as a monofunctional DNA alkylator by analogy with the glutathione conjugates of 1,2-dihaloalkanes. The lack of sensitivity of Salmonella TA100 towards formaldehyde (Schmid et al., Mutagenesis, 1 (1986) No. 6, 427-431) suggests that GSCH2Cl is responsible for methylene chloride mutagenicity in Salmonella. In Escherichia coli K12 (AB1157), formaldehyde was mutagenic only in the wild-type, a characteristic shared with cross-linking agents, whereas 1,2-dibromoethane (1,2-DBE) was more mutagenic in uvrA cells (AB1886). Methylene chloride, activated by S9 from mouse liver, was mutagenic only in wild-type cells, suggesting a mutagenic role for metabolically derived formaldehyde in E. coli. Mouse-liver S9 also enhanced the cell-killing effect of methylene chloride in the uvrA, and a recA/uvrA double mutant (AB2480) which is very sensitive to DNA damage. This pattern was consistent with formaldehyde damage. However, a mutagenic role in bacteria for the glutathione conjugate of methylene chloride cannot be ruled out by these E. coli experiments because S9 fractions did not increase 1,2-DBE mutagenicity, suggesting lack of cell wall penetration by this reactive species. Rat-liver S9 did not activate methylene chloride to a bacterial mutagen or enhance methylene chloride-induced cell-killing, which is consistent with the carcinogenicity difference between the species. |
| Doi | 10.1016/0165-1218(94)90050-7 |
| Pmid | 7508089 |
| Wosid | WOS:A1994MU51700008 |
| Url | http://www.sciencedirect.com/science/article/pii/0165121894900507 |
| Is Certified Translation | No |
| Dupe Override | No |
| Comments | Source: Web of Science WOS:A1994MU51700008 |
| Is Public | Yes |
| Language Text | English |
| Keyword | METHYLENE CHLORIDE; FORMALDEHYDE; GLUTATHIONE; 1,2-DIBROMOETHANE; ESCHERICHIA COLI; SALMONELLA TYPHIMURIUM |
| Is Peer Review | Yes |
| Relationship(s) |
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