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GENOTOXICITY OF 1,3-DICHLOROPROPANE, 2,2-DICHLOROPROPANE, AND 1,1-DICHLOROPROPENE IN SALMONELLA, THE E. COLI PROPHAGE-INDUCTION ASSAY, AND HUMAN HEPH2 CELLS
Citation:
Granville, C. A., S H. Warren, G. HugginsClark, S E. George, L D. Claxton, AND D M. DeMarini. GENOTOXICITY OF 1,3-DICHLOROPROPANE, 2,2-DICHLOROPROPANE, AND 1,1-DICHLOROPROPENE IN SALMONELLA, THE E. COLI PROPHAGE-INDUCTION ASSAY, AND HUMAN HEPH2 CELLS. Presented at Environmental Mutagen Society, Anchorage, Alaska, 4/27/02--5/2/02.
Description:
Genotoxicity of 1,3-Dichloropropane, 2,2-Dichloropropane, and 1,1-Dichloropropene in Salmonella, the E. coli Prophage-Induction Assay and Human HepG2 Cells
1,3-Dichloropropane (1,3-DCP), 2,2-dichloropropane (2,2-DCP), and 1,1- dichloropropene ( 1,1- DCP) have been detected in source waters (both ground and surface) across he country at levels ranging from 0.0001 ug/L to 61ug/L. Their introduction to the environment probably occurs through soil fumigants. Despite their structural similarity to 1,3- dichloropropene, a rodent carcinogen, there is no data for the genotoxicity or carcinogenicity of hese chemicals. As a result, these compounds were placed on the 1998 US EP A Contaminant Candidate List and deemed "high priority for research " in 1999. Thus, the genotoxicity of these cmpounds is being studied in Salmonella, the E. coli prophage-induction assay, and in human HepG2 cells. Our results in the prophage-induction assay show that 1, I-DCP is genotoxic in the presence of S9, whereas; 1,3-DCP and 2,2-DCP are weakly genotoxic without S9. These chemicals were also tested in Salmonella strains TA98, TAI00, TA104, TA1535, RSJ100 and JST -TI (T A 1535 expressing the human GST- TI gene ). The results were largely negative. Only ,1-DCP was mutagenic and only in RSJI00. These results suggest different mechanisms for the mutagenicity of these three compounds: 1,3-DCP and 2,2-DCP can cause DNA damage that induces prophage without metabolic activation; 1, l-DCP , on the other hand, can induce prophage and revert Salmonella. Thus, 1,3-DCP and 2,2-DCP may cause DNA strand breaks, which would induce prophage, but would not revert the Salmonella strains used in this study. 1,1- DCP , on the other hand, may be activated to a base-substitution mutagen by the rat GST -theta enzyme, but not by the homologous human enzyme. Preliminary results from the comet assay show that ,1-DCP is a less potent cytotoxin than 1,3-dichloropropene, but that it can still cause strand breaks. Comparative gene expression analysis is also being planned using Clontech AtlasTM microarrays.
Abstract does not necessarily represent policy of the US EP A.