Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0345904 (liver cancer)
 15,188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dichloroacetic acid (DCA) and trichloroacetic acid (TCA) are major metabolites of tetrachloroethylene (PCE) and trichloroethylene (TCE) and are found in chlorinated drinking water. All four chlorinated compounds are liver carcinogens in B6C3F1 mice. It has previously been reported that approximately 20% of hepatic tumors induced by PCE exhibited loss of heterozygosity (LOH) on chromosome 6, suggesting the presence of a tumor suppressor gene. In the current investigation, we determined whether TCA or DCA also induced LOH on chromosome 6. Liver tumors were initiated in 15 day old female B6C3F1 mice with N-methyl-N-nitrosourea (MNU) and promoted with 20 mmol/l DCA or TCA in their drinking water. Twenty-four and thirty-seven liver tumors promoted by DCA and TCA, respectively, were examined for LOH using 4 polymorphic loci on chromosome 6. Ten of 37 (27%) tumors (7 of 27 carcinomas and 3 of 10 adenomas) promoted by TCA exhibited LOH at least for two loci on chromosome 6. All 10 tumors that exhibited LOH, lost the C57BL/6J allele at both the D6mit9 loci, while two also lost at least one of the C3H/HeJ alleles. No LOH on chromosome 6 was observed in the 24 liver tumors promoted by DCA. The LOH on chromosome 6 in TCA but not in DCA-promoted tumors supports it as an active metabolite of PCE and demonstrates different pathogenesis at least for some of the DCA and TCA-promoted liver cancer.
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PMID:Loss of heterozygosity on chromosome 6 in dichloroacetic acid and trichloroacetic acid-induced liver tumors in female B6C3F1 mice. 897 3

Tetrachloroethene (PCE), a common industrial solvent and environmental contaminant, is primarily used in the dry-cleaning industry. The toxicity of PCE has been linked to vision disorders, renal and hepatic cancer, and autoimmune diseases. Although the mechanism of toxicity is not fully understood, PCE forms trichloroacylated protein adducts in tissues where toxicity is known to occur. These adducts may be responsible for toxicity by altering the function of cellular proteins. Using Western blot analysis, formation of trichloroacylated protein adducts has been reported. To determine the localization of the adducts in a specific zone of a tissue, immunohistochemical staining was used in the study. An antiserum to trichloroacylated proteins was raised in rabbits and its specificity was established by enzyme-linked immunosorbent assay (ELISA). Female MRL-lpr/lpr and MRL +/+ mice were treated with PCE using a single 5-mmol/kg dose over 24 h or on every fourth day for 6 wk (total 20 doses). Formation of trichloroacylated protein adducts was observed in the liver, and localized to the centrilobular zones. Intensity and circumference of the staining around the central vein were much greater in subchronically treated mice than in acutely treated mice. No immunochemical reactivity was observed in any of the other tissues examined. This study shows that hepatic trichloroacylated protein adducts are localized in a region of the liver where PCE-mediated toxicity is known to occur. Immunohistochemical localization of these adducts and its association with PCE-induced toxicity support the contention that adducts may contribute to toxicity.
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PMID:Immunohistochemical localization of trichloroacylated protein adducts in tetrachloroethene-treated mice. 1139