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Interactions of trichloroethylene with DNA in vitro and with RNA and DNA of various mouse tissues in vivo

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Abstract

The covalent binding of14C-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 with14C-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 with14C-TRI in the absence of liver microsomes. Covalent binding of14C-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 with14C-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 with14C-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 of14C-TRI. The radioactivity in RNA increased in the order brain < testis < pancreas < kidney < liver < lung < spleen. The radioactivity in DNA increased in the order brain < kidney < testis < lung < pancreas < liver < 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.

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References

  • Allemand H, Pessayre D, Descatoire V, Degott C, Feldman G, Benhamou J-P (1978) Metabolie activation of trichloroethylene into a chemically reactive metabolite toxic to the liver. J Pharmacol Exp Ther 204: 714–723

    Google Scholar 

  • Axelson O, Andersson K, Hogstedt C, Holmberg B, Molina G, de Verdier A (1978) A cohort study on trichloroethylene exposure and cancer mortality. J Occup Med 20: 194–196

    Google Scholar 

  • Baden JM, Simmon VF (1980) Mutagenic effects of inhalational anesthetics. Mutat Res 75: 169–189

    Google Scholar 

  • Banerjee S, Van Duuren BL (1978) Covalent binding of the carcinogen trichloroethylene to hepatic microsomal proteins and to exogenous DNA in vitro. Cancer Res 38: 776–780

    Google Scholar 

  • Bergman K (1979) Whole-body autoradiography and allied tracer techniques in distribution and elimination studies of some organic solvents. Scand J Work Environ Health (Suppl 1) 5: 189–216

    Google Scholar 

  • Bergman K (1982) Reactions of vinyl chloride with RNA and DNA of various mouse tissues in vivo. Arch Toxicol 49: 117–129

    Google Scholar 

  • Bolt HM, Filser JG (1977) Irreversible binding of chlorinated ethylenes to macromolecules. Environ Health Perspect 21: 107–112

    Google Scholar 

  • Bolt HM, Laib RJ, Filser JG (1982) Reactive metabolites and carcinogenicity of halogenated ethylenes. Biochem Pharmacol 31: 1–4

    Google Scholar 

  • Bonse G, Henschler D (1976) Chemical reactivity, biotransformation and toxicity of polychlorinated aliphatic compounds. CRC Crit Rev Toxicol 10: 395–409

    Google Scholar 

  • Burton K (1956) A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem J 62: 315–323

    Google Scholar 

  • DiRenzo AB, Gandolfi AJ, Sipes IG (1982) Microsomal bioactivation and covalent binding of aliphatic halides to DNA. Toxicol Lett 11: 243–252

    Google Scholar 

  • Docks EL, Krishna G (1975) Covalent binding of trans-stilbene to rat liver microsomes. Biochem Pharmacol 24: 1965–1969

    Google Scholar 

  • Green T, Hathway DE (1978) Interactions of vinyl chloride with rat liver DNA in vivo. Chem Biol Interact 22: 211–224

    Google Scholar 

  • Gu ZW, Sele B, Chmara D, Jalbert P, Vincent M, Vincent F, Marka C, Faure J (1981) Effects du trichloréthylène et de ses métabolites sur le taux d'échanges de chromatides-soers. Ann Genet 24: 105–106

    Google Scholar 

  • Hathway DE (1980) Consideration of the evidence for mechanisms of 1,1,2-trichloroethylene metabolism, including new identification of its dichloroacetic acid and trichloroacetic acid metabolites in mice. Cancer Lett 8: 263–269

    Google Scholar 

  • Henschler D, Eder E, Neudecker T, Metzler M (1977) Carcinogenicity of trichloroethylene: fact or artifact? Arch Toxicol 37: 233–236

    Google Scholar 

  • Henschler D, Hoos WR, Fetz H, Dallmeier E, Metzler M (1979) Reactions of trichloroethylene epoxide in aqueous systems. Biochem Pharmacol 28: 543–548

    Google Scholar 

  • Henschler D, Romen W, Elsässer HM, Reichert D, Eder E, Radwan Z (1980) Carcinogenicity study of trichloroethylene by longterm inhalation in three animal species. Arch Toxicol 43: 237–248

    Google Scholar 

  • International Agency for Research on Cancer (1976) IARC Monographs on the evaluation of the carcinogenic risk of chemicals to humans, vol 11. Lyon, pp 263–276

    Google Scholar 

  • Irving CC, Veazey RA (1968) Isolation of deoxyribonucleic acid and ribosomal ribonucleic acid from rat liver. Biochim Biophys Acta 166: 246–248

    Google Scholar 

  • Kline SA, Van Duuren BL (1977) Reactions of epoxy-1,1,2-trichloroethane with nucleophiles. J Heterocycl Chem 14: 455–458

    Google Scholar 

  • Konietzko H, Haberlandt W, Heilbronner H, Reill G, Weichardt H (1978) Cytogenetische Untersuchungen an Trichloräthylen-Arbeitern. Arch Toxicol 40: 201–206

    Google Scholar 

  • Laib RJ, Bolt HM (1978) Formation of 3,N4-ethenocytidine moieties in RNA by vinyl chloride metabolites in vitro and in vivo. Arch Toxicol 39: 235–240

    Google Scholar 

  • Laib RJ, Stöckle G, Bolt HM, Kunz W (1979) Vinyl chloride and trichloroethylene: comparison of alkylating effects of metabolites and induction of preneoplastic enzyme deficiences in rat liver. J Cancer Res Clin Oncol 94: 139–147

    Google Scholar 

  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193: 265–275

    Google Scholar 

  • Miller RE, Guengerich FP (1982) Oxidation of trichloroethylene by liver microsomal cytochrome P-450: evidence for chlorine migration in a transition state not involving trichloroethylene oxide. Biochemistry 21: 1090–1097

    Google Scholar 

  • Miller RE, Guengerich FP (1983) Metabolism of trichloroethylene in isolated hepatocytes, microsomes, and reconstituted enzyme systems containing cytochrome P-450. Cancer Res 43: 1145–1152

    Google Scholar 

  • NCI Carcinogenesis Bioassay of Trichloroethylene (1976) National Cancer Institute Technical Report Series No. 2, US Dept. Health, Education and Welfare, DHEW Publ. No. (NIH) 76-802, Washington DC

  • O'Connor PJ, Margison GP, Craig AW (1975) Phosphotriesters in rat liver deoxyribonucleic acid after the administration of the carcinogen N,N-dimethylnitrosamine in vivo. Biochem J 145: 475–482

    Google Scholar 

  • Parchman LG, Magee PN (1982) Metabolism of (14C)trichloroethylene to14CO2 and interaction of a metabolite with liver DNA in rats and mice. J Toxicol Environ Health 9: 797–813

    Google Scholar 

  • Pelkonen O, Boobis AR, Yagi H, Jerina DM, Nebert DW (1978) Tentative identification of benzo(a)pyrene metabolite-nucleoside complexes produced in vitro by mouse liver microsomes. Mol Pharmacol 14: 306–322

    Google Scholar 

  • Perocco P, Prodi G (1981) DNA damage by haloalkanes in human lymphocytes cultured in vitro. Cancer Lett 13: 213–218

    Google Scholar 

  • Price P, Hassett CM, Mansfield JI (1978) Transforming activities of trichloroethylene and proposed industrial alternatives. In Vitro 14: 290–293

    Google Scholar 

  • Schneider WC (1957) Determination of nucleic acids in tissues by pentose analysis. Methods Enzymol 3: 680–684

    Google Scholar 

  • Stott WT, Quast JF, Watanabe PG (1982) The pharmacokinetics and macromolecular interactions of trichloroethylene in mice and rats. Toxicol Appl Pharmacol 62: 137–151

    Google Scholar 

  • Sun L, Singer B (1975) The specificity of different classes of ethylating agents toward various sites of HeLa cell DNA in vitro and in vivo. Biochemistry 14: 1795–1802

    Google Scholar 

  • Uehleke H, Poplawski-Tabarelli S (1977) Irreversible binding of14C-labelled trichloroethylene to mice liver constituents in vivo and in vitro. Arch Toxicol 37: 289–294

    Google Scholar 

  • Uehleke H, Tabarelli-Poplawski S, Bonse G, Henschler D (1977) Spectral evidence for 2,2,3-trichlorooxirane formation during microsomal trichloroethylene oxidation. Arch Toxicol 37: 95–105

    Google Scholar 

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  1. Kerstin Bergman

    Present address: Toxicology Laboratory, National Food Administration, Box 622, S-751 26, Uppsala, Sweden

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  1. Department of Toxicology, Uppsala University, Box 573, S-751 23, Uppsala, Sweden

    Kerstin Bergman

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Bergman, K. Interactions of trichloroethylene with DNA in vitro and with RNA and DNA of various mouse tissues in vivo. Arch Toxicol 54, 181–193 (1983). https://doi.org/10.1007/BF01239202

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  • DOI: https://doi.org/10.1007/BF01239202

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