Interactions of trichloroethylene with DNA in vitro and with RNA and DNA of various mouse tissues in vivo.
The covalent binding of 14C-1,1,2-trichloroethylene (14C-TRI) metabolites to calf thymus DNA in vitro and to RNA and DNA of mouse brain, lung, liver, kidney, spleen, pancreas, and testis after repeated i.p. injections has been studied. Hydrolysates of DNA reacted with 14C-TRI in vitro and hydrolysates of RNA and DNA from selected organs were separated on Aminex A6 for quantitation of alkylation products. The presence of 3,N4-etheno(deoxy)cytidine, 1,N6-etheno(deoxy)adenosine and 1,N6-ethenoadenine was investigated. No radioactivity could be registered in DNA incubated with 14C-TRI in the absence of liver microsomes. Covalent binding of 14C-TRI to DNA took place in the presence of liver microsomes from control mice. The binding was enhanced by 50% if liver microsomes from phenobarbital pretreated mice were used. The radioactivity in DNA reacted with 14C-TRI and microsomes from control mice was eluted in early fractions and together with thymidine. The same two peaks appeared on chromatography of DNA incubated with 14C-TRI and liver microsomes from phenobarbital pretreated mice. In addition, radioactivity was eluted together with 1,N6-ethenoadenine. Radioactivity was registered in RNA and DNA from all of the studied organs after i.p. injections of 14C-TRI. The radioactivity in RNA increased in the order brain less than testis less than pancreas less than kidney less than liver less than lung less than spleen. The radioactivity in DNA increased in the order brain less than kidney less than testis less than lung less than pancreas less than liver less than spleen. Aminex A6 chromatography revealed that the entire radioactivity in RNA from liver and kidney and in DNA from kidney, testis, lung, pancreas, and spleen was due to metabolic incorporation, particularly into guanine and adenine. This finding indicates that the C-C bond in TRI is split, with the formation of C1-fragments, during biotransformation in vivo. In liver DNA, the metabolic incorporation of radioactivity was insignificant. Instead, the dominant part of the radioactivity in liver DNA was eluted in early fractions. The elution profile of radioactivity in liver DNA gave no direct evidence of the formation of TRI-DNA adducts in vivo. No etheno-derivatives were identified as alkylation products of TRI in vivo, which is consistent with current theories of the metabolic fate of TRI.
D000478:Alkylation; D000818:Animals; D002250:Carbon Radioisotopes; D002417:Cattle; D002852:Chromatography, Ion Exchange; D004247:DNA / Q000378:metabolism*; D004347:Drug Interactions; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism*; D009696:Nucleic Acids / Q000378:metabolism; D012313:RNA / Q000378:metabolism*; D013949:Thymus Extracts / Q000378:metabolism; D014018:Tissue Distribution; D014241:Trichloroethylene / Q000378:metabolism*
D002250:Carbon Radioisotopes; D009696:Nucleic Acids; D013949:Thymus Extracts; D014241:Trichloroethylene; D012313:RNA; D004247:DNA