Health & Environmental Research Online (HERO)


Print Feedback Export to File
632764 
Journal Article 
Loss of heterozygosity on chromosome 6 in dichloroacetic acid and trichloroacetic acid-induced liver tumors in female B6C3F1 mice 
Tao, L; Li, K; Kramer, PM; Pereira, MA 
Yes 
Cancer Letters
ISSN: 0304-3835
EISSN: 1872-7980 
108 
2 
257-261 
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 
10; 13425-80-4; 4; 6; 7; 76-03-9; Active; Adenoma; Alleles; Animals; Cancer; carcinogen; Carcinogens; Carcinoma; Carcinomas; chemically induced; Chlorinated; Chromosome Deletion; Dichloroacetate; Drinking; Drinking water; Experimental; Female; genetics; Humans; Inbred C3H; Inbred C57BL; Liver; Liver cancer; Liver Neoplasms; Liver tumors; Medical; metabolites; Mice; Ohio; pathology; PCE; Support; Tetrachloroethylene; Toxicity; Trichloroacetic Acid; Trichloroethylene; Tumor; Tumor Suppressor; USA; Water