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DNA-binding assay of methyl chloride

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Abstract

Fischer-344 rats and B6C3F1 mice of both sexes were exposed in closed chambers to 14C-labeled methyl chloride. Different clearance values from the gas phase of the system indicated that, based on body weight, mice metabolized the test compound much faster than rats. After isolation of DNA and nucleoproteins from liver and kidneys radioactivity was found in all macromolecular samples; this was ascribed to metabolic C1-incorporation. Radioactivity incorporation was particularly high in DNA of mouse kidneys, suggesting a high turnover to active C1 bodies (formaldehyde, formate) in this tissue.

Analyses of DNA samples from kidneys of female and male mice showed neither 7-N-methylguanine nor O6-methylguanine. Hence, the formation of tumors in B6C3F1 mice exposed to high concentrations of methyl chloride is not based on methylation of DNA in this tissue.

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References

  • Andrews AW, Zawistowski ES, Valentine CR (1976) A comparison of the mutagenic properties of vinyl chloride and methyl chloride. Mutation Res 40: 273–276

    Google Scholar 

  • Bartsch H, Terracini B, Malaveille C, Tomatis L, Wahrendorf J, Brun G, Dodet B (1983) Quantitative comparison of carcinogenicity, mutagenicity and electrophilicity of 10 direct-acting agents and of the initial O6:7-N-alkylguanine ratio in DNA with carcinogenic potency in rodents. Mutation Res 110: 181–219

    Google Scholar 

  • Battelle Columbus Laboratories (1981) Final report on a chronic inhalation toxicology study in rats and mice exposed to methyl chloride submitted to Chemical Industry Institute of Toxicology, Vol. 1–4

  • Bloom KS, Anderson JN (1978) Fractionation and characterization of chromosomal proteins by the hydroxylapatite dissociation method. J Biol Chem 253: 4446–4450

    Google Scholar 

  • Bolt HM, Kappus H, Buchter A, Bolt W (1976) Disposition of l,2-14C-vinyl chloride in the rat. Arch Toxicol 35: 153–162

    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 

  • Bus JS (1982) Integrated studies of methyl chloride toxicity. CIIT Activities 2(1): 3–4

    Google Scholar 

  • Dodd DE, Bus JS, Barrow CS (1982) Non-protein sulfyhdryl alterations in F-344 rats following acute methyl chloride inhalation. Toxicol Appl Pharmacol 62: 228–236

    Google Scholar 

  • Van Doorn R, Borm PJA, Leijdeckers CM, Henderson PT, Reuvers J, van Bergen TJ (1980) Detection and identification of S-methylcysteine in urine of workers exposed to methyl chloride. Int Arch Occup Environ Hlth 46: 99–109

    Google Scholar 

  • Filser JG, Bolt HM (1979) Pharmacokinetics of halogenated ethylenes in rats. Arch Toxicol 42: 123–136

    Google Scholar 

  • Filser JG, Bolt HM (1981) Inhalation pharmacokinetics based on gas uptake studies. I. Improvement of kinetic models. Arch Toxicol 47: 279–292

    Google Scholar 

  • Giles KW, Myers A (1965) An improved diphenylamine method for the estimation of deoxyribonucleic acid. Nature 206: 93

    Google Scholar 

  • Kornbrust DJ, Bus JS (1982) Metabolism of methyl chloride to formate in rats. Toxicol Appl Pharmacol 65: 135–143

    Google Scholar 

  • Kornbrust DJ, Bus JS (1984) Glutathione depletion by methyl chloride and association with lipid peroxidation in mice and rats. Toxicol Appl Pharmacol 72: 388–399

    Google Scholar 

  • Kornbrust DJ, Bus J, Doerjer G, Swenberg JA (1982) Association of inhaled 14C-methyl chloride with macromolecules from various rat tissues. Toxicol Appl Pharmacol 65: 122–134

    Google Scholar 

  • Laib RJ, Bolt HM (1977) Alkylation of RNA by vinyl chloride metabolites in vitro and in vivo: formation of 1-N6-ethenoadenosine. Toxicology 8: 185–195

    Google Scholar 

  • Landry TD, Gushow TS, Langvaardt PW, Wall JM, McKenna MJ (1983) Pharmacokinetics and metabolism of inhaled methyl chloride in the rat and dog. Toxicol Appl Pharmacol 68: 473–486

    Google Scholar 

  • Lawley PD (1979) Approaches to chemical dosimetry in mutagenesis and carcinogenesis: the relevance of reactions of chemical mutagens and carcinogens with DNA. In: Chemical Carcinogens and DNA, ed. Grover, PL. Vol. I, CRC Press, Boca Raton, Fl, pp 1–36

    Google Scholar 

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

    Google Scholar 

  • Lutz WK (1979) In vivo covalent binding of organic chemicals to DNA as a quantitative indicator in the process of chemical carcinogenesis. Mutation Res 65: 289–356

    Google Scholar 

  • Repko R, Lasley SM 1979 Behavioral, neurological and toxic effects of methyl chloride: a review of the literature. CRC Crit Rev Toxicol Nov. 1979, pp 283–302

  • Rickwood D, Birnie GD (1976) Preparation, characterization and fractionation of chromatin. In: Birnie GD (ed) Subnuclear Components. Preparation and Fractionation. Butterworths, London-Boston, pp 129–180

    Google Scholar 

  • Simmon VF, Kauhanen K, Mortelmans K, Tardiff R (1978) Mu-tagenic activity of chemicals identified in drinking water. Mutation Res 53: 129

    Google Scholar 

  • Swenberg JA, Barrow CS, Heck HDA, Levine RJ, Morgan KT, Starr TB (1983) Non-linear biological responses to formaldehyde and their implications for carcinogenic risk assessment. Carcinogenesis 4: 945–952

    Google Scholar 

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Peter, H., Laib, R.J., Ottenwälder, H. et al. DNA-binding assay of methyl chloride. Arch Toxicol 57, 84–87 (1985). https://doi.org/10.1007/BF00343115

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  • DOI: https://doi.org/10.1007/BF00343115

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