DNA sequence analysis of methylene chloride-induced HPRT mutations in Chinese hamster ovary cells: Comparison with the mutation spectrum obtained for 1,2-dibromoethane and formaldehyde
Graves, RJ; Trueman, P; Jones, S; Green, T
HERO ID
626446
Reference Type
Journal Article
Year
1996
Language
English
PMID
| HERO ID | 626446 |
|---|---|
| In Press | No |
| Year | 1996 |
| Title | DNA sequence analysis of methylene chloride-induced HPRT mutations in Chinese hamster ovary cells: Comparison with the mutation spectrum obtained for 1,2-dibromoethane and formaldehyde |
| Authors | Graves, RJ; Trueman, P; Jones, S; Green, T |
| Journal | Mutagenesis |
| Volume | 11 |
| Issue | 3 |
| Page Numbers | 229-233 |
| Abstract | Glutathione-S-transferase-mediated metabolism of methylene chloride (MC) generates S-chloromethylglutathione, which has the potential to react with DNA, and formaldehyde, which is a known mutagen. MC-induced mutations in the HPRT gene of Chinese hamster ovary cells have been sequenced and compared with the mutations induced by 1, 2-dibromoethane (1,2-DEB), which is known to act through a glutathione conjugate, and formaldehyde. All three compounds induced primarily point mutations, with a small number of insertion and deletion events. The most common point mutations induced by MC were GC-->AT transitions (4/8), with two GC-->CG transversions and two AT-->TA transversions. This pattern of mutations showed greater similarity with 1,2-DBE, where the dominant point mutations were GC-->AT transitions (7/9), than formaldehyde, where all mutations were single base transversions and 5/6 occurred from AT base pairs. The mutation sequence results for MC suggest that S-chloromethylglutathione plays a major role in MC mutagenesis, with only a limited contribution from formaldehyde. The involvement of a glutathione (GSH) conjugate in MC mutagenicity would be analogous to the well-characterized pathway of activation of 1,2-DBE. |
| Doi | 10.1093/mutage/11.3.229 |
| Pmid | 8671744 |
| Wosid | WOS:A1996UK07200002 |
| Url | https://www.proquest.com/scholarly-journals/dna-sequence-analysis-methylene-chloride-induced/docview/15620645/se-2?accountid=171501 |
| Is Certified Translation | No |
| Dupe Override | No |
| Comments | Source: Web of Science WOS:A1996UK07200002 |
| Is Public | Yes |
| Language Text | English |
| Keyword | <?xml version="1.0" encoding="UTF-8"?><kw>Cytology and Cytochemistry-Animal</kw>; <?xml version="1.0" encoding="UTF-8"?><kw>Genetics and Cytogenetics-Animal</kw>; <?xml version="1.0" encoding="UTF-8"?><kw>Biochemical Studies-General</kw>; <?xml version="1.0" encoding="UTF-8"?><kw>Biochemical Studies-Nucleic Acids</kw>; <?xml version="1.0" encoding="UTF-8"?><kw>Toxicology-General</kw>; <?xml version="1.0" encoding="UTF-8"?><kw>Cricetidae</kw> |
| Is Peer Review | Yes |
| Relationship(s) |
|