The frequency and spectrum of H-ras oncogene activation by the water disinfection by products 2-chloroacetaldehyde (107200) (CAA), chloral-hydrate (302170) (CH), and dichloroacetic-acid (79436) (DCA) was investigated in the livers of male B6C3F1-mice. Mice had been administered high doses of these chemicals over a 2 year period. No mutations were noted in the H-ras oncogene in any normal liver tissue samples taken from mice with hepatocellular carcinomas. Codon 12/13 mutations were not present in any samples of either tumor tissues or normal liver. A relatively low frequency of H-ras activation was noted for liver tumors in mice dosed with CAA. For mice administered CH, a very low frequency of H-ras activation was found for liver tumors. A higher frequency of H-ras mutation was found for liver tumors in mice administered DCA. The authors conclude that the induction of the hepatocellular carcinomas by CAA does not involve the activation of the H-ras oncogene. The authors suggest that while DCA is most likely not directly causing these H- ras mutations, the proliferative action of DCA on the liver may be preferentially promoting cells containing ras mutations.
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