Ras proto-oncogene activation in dichloroacetic acid-, trichloroethylene- and tetrachloroethylene-induced liver tumors in B6C3F1 mice
Anna, CH; Maronpot, RR; Pereira, MA; Foley, JF; Malarkey, DE; Anderson, MW
HERO ID
628762
Reference Type
Journal Article
Year
1994
Language
English
PMID
| HERO ID | 628762 |
|---|---|
| In Press | No |
| Year | 1994 |
| Title | Ras proto-oncogene activation in dichloroacetic acid-, trichloroethylene- and tetrachloroethylene-induced liver tumors in B6C3F1 mice |
| Authors | Anna, CH; Maronpot, RR; Pereira, MA; Foley, JF; Malarkey, DE; Anderson, MW |
| Journal | Carcinogenesis |
| Volume | 15 |
| Issue | 10 |
| Page Numbers | 2255-2261 |
| Abstract | The frequency and mutation spectra of proto-oncogene activation in hepatocellular neoplasms induced by tetrachloroethylene, trichloroethylene and dichloroacetic acid were examined to help define the molecular basis for their carcinogenicity. H-ras codon 61 activation was not significantly different among dichloroacetic acid- and trichloroethylene-induced and combined historical and concurrent control hepatocellular tumors (62%, 51% and 69% respectively). The mutation spectra of H-ras codon 61 mutations showed a significant decrease in AAA and increase in CTA mutations for dichloroacetic acid- and trichloroethylene-induced tumors when compared to combined controls. The H-ras codon 61 mutation frequency for tetrachloroethylene-induced tumors was significantly lower (24%) than that of combined controls and also that of the two other chemicals. Mutations at codons 13 and 117 plus a second exon insert contributed 4% to the total H-ras frequencies for trichloroethylene and tetrachloroethylene. There was also a higher incidence of K-ras activation (13%) in tetrachloroethylene-induced tumors than in the other chemically induced or control tumors. Four liver tumors were found to contain insertions of additional bases within the second exon of K- or H-ras. These findings suggest that exposure to dichloroacetic acid, trichloroethylene and tetrachloroethylene provides a selective growth advantage to spontaneously occurring mutations in codon 61 of H-ras and, at the same time, is responsible for a small number of unique molecular lesions suggestive of either a random genotoxic mode of action or a non-specific result of secondary DNA damage. However, the absence of ras activation in many of the liver neoplasms suggests that alternative mechanisms are also important in B6C3F1 mouse hepatocarcinogenesis. |
| Doi | 10.1093/carcin/15.10.2255 |
| Pmid | 7955063 |
| Is Certified Translation | No |
| Dupe Override | No |
| Comments | "ras" in title is italicized |
| Is Public | Yes |
| Language Text | English |
| Keyword | <?xml version="1.0" encoding="UTF-8"?><kw>DCN-223628</kw>; <?xml version="1.0" encoding="UTF-8"?><kw>Carcinogenicity</kw>; <?xml version="1.0" encoding="UTF-8"?><kw>Chlorinated ethylenes</kw>; <?xml version="1.0" encoding="UTF-8"?><kw>Laboratory animals</kw>; <?xml version="1.0" encoding="UTF-8"?><kw>Molecular biology</kw>; <?xml version="1.0" encoding="UTF-8"?><kw>Liver tumors</kw>; <?xml version="1.0" encoding="UTF-8"?><kw>Gene mutation</kw>; <?xml version="1.0" encoding="UTF-8"?><kw>Oncogenic agents</kw>; <?xml version="1.0" encoding="UTF-8"?><kw>Liver cancer</kw>; <?xml version="1.0" encoding="UTF-8"?><kw>Chlorinated hydrocarbons</kw> |
| Is Qa | No |