期刊
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
卷 572, 期 1-2, 页码 98-112出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.mrfmmm.2004.12.009
关键词
1.1-dichloropropene; GSTT1-1; mutagenicity; metabolism; Salmonella
资金
- PHS HHS [F3211111-03] Funding Source: Medline
1, 1 -Dichloropropene (1, 1 -DCPe) is a contaminant of some source waters used to make drinking water. Because of this and the fact that no toxicological data were available for this compound, which is structurally similar to the rodent carcinogen 1,3-dichloropropene (1,3-DCPe), 1,1-DCPe was placed on the Contaminant Candidate List of the US Environmental Protection Agency. Consequently, we have performed a hazard characterization of 1,1-DCPe by evaluating its mutagenicity in the Salmonella assay and its DNA damaging (comet assay) and apoptotic (caspase assay) activities in human lymphoblastoid cells. In Salmonella, 1,1-DCPe was not mutagenic in strains TA98, TA100, TA1535, or TA104 +/- S9 mix. However, it was clearly mutagenic in strain RSJ100, which expresses the rat GSTF1-1 gene. 1,1-DCPe did not induce DNA damage in GSTT1-1-deficient human lymphoblastoid cells, and it induced apoptosis in these cells only at 5 mM. Consistent with its mutagenesis in RSJ100, 1,1-DCPe reacted with glutathione (GSH) in vitro, suggesting an addition-elimination mechanism to account for the detected GSH conjugate. 1,1-DCPe was similar to 5000 times more mutagenic than its ethene congener 1,1-dichloroethylene (1,1-DCE or vinylidene chloride). Neither 1,3-DCE nor 1,3-DCPe showed enhanced mutagenicity in strain RSJ100, indicating a lack of activation of these congeners by GSTT1-1. Thus, 1,1-DCPe is a base- substitution mutagen requiring activation by GSTT1-1, possibly involving the production of a reactive episulfonium ion. This bioactivation mechanism of 1,1-DCPe is different from that of its congeners 1,1-DCE and 1, 3 -DCPe. The presence of 1,1-DCPe in source waters could pose an ecological or human health risk. Occurrence data for 1,1DCPe in finished drinking water are needed to estimate human exposure to, and possible health risks from, this mutagenic compound.
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