Abstract
Groups of industrial and laboratory chemicals were tested for their alkylation activity using 4-(p-nitrobenzyl)-pyridine and deoxyguanosine as nucleophiles. The alkylation activity was compared with mutagenicity of the chemicals to E. coli WP2 uvrA without metabolic activation. All the epoxide-containing compounds including simple epoxides and glycidyl ethers elicited alkylation activity and mutagenicity. Furthermore there was a reasonable correlation between the rate of alkylation and the mutagenic potency. All the methylating and ethylating compounds tested were active but no correlation was observed between the rate of alkylation and the mutagenic potency, apparently due to the different types of alkylation products formed. The other compounds tested including halogenated hydrocarbons, hydrazine derivatives, aldehydes, thiuram and dithiocarbamate derivatives elicited a slow or no alkylation activity while many of the compounds were mutagenic. There was no evidence among the chemicals tested of an alkylating non-mutagen. Thus evidence of alkylation activity appears to indicate mutagenic risk.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Abbott PJ, Saffhill R (1979) DNA synthesis with methylated poly(dC-dG) templates. Evidence for a competitive nature to miscoding by O6-methylguanine. Biochim Biophys Acta 562: 51–59
Andersen M, Kiel P, Larsen H, Maxild J (1978) Mutagenic action of aromatic epoxy resins. Nature 276: 391–392
Barbin A, Brésil H, Groisy A, Jacquignon P, Malaveille C, Montesano R, Bartsch H (1975) Liver microsome-mediated formation of alkylating agents from vinyl bromide and vinyl chloride. Biochem Biophys Res Commun 67: 596–603
Bartsch H, Malaveille C, Tierney B, Grover PL, Sims P (1979) The association of bacterial mutagenicity of hydrocarbon-derived ‘bay-region’ dihydrodiols with the Iball indices for carcinogenicity and with the extents of DNA-binding on mouse skin of the parent hydrocarbons. Chem Biol Interact 26: 185–196
Epstein J, Rosenthal RW, Ess RJ (1955) Use of γ-(4-nitrobenzyl)pyridine as analytical reagent for ethyleneimines and alkylating agents. Anal Chem 27: 1435–1439
Fishbein L (1979) Potential industrial carcinogens and mutagens. In: Studies in environmental science, no 4. Elsevier, Amsterdam, p 534
Green MHL, Muriel WJ (1976) Mutagen testing using Trp+ reversion in Escherichia coli. Mutat Res 38: 3–32
Hedenstedt A, Rannug U, Ramel C, Wachtmeister CA (1979) Mutagenicity and metabolism studies on 12 thiuram and dithiocarbamate compounds used as accelerators in the Swedish rubber industry. Mutat Res 68: 313–321
Heidelberger C (1975) Chemical carcinogenesis. Annu Rev Biochem 44: 79–121
Hemminki K (1979) Fluorescence study of DNA alkylation by epoxides. Chem Biol Interact 28: 269–278
Hemminki K, Falck K (1979) Correlation of mutagenicity and 4-(p-nitrobenzyl)-pyridine alkylation by epoxides. Toxicol Lett 4: 103–106
Hemminki K, Paasivirta J, Kurkirinne T, Virkki L (1980) Alkylation products of DNA bases by simple epoxides. Chem Biol Interact 30: 259–270
Kadlubar FF, Miller JA, Miller EC (1978) Guanyl O6-aryl-amination and O6-arylation of DNA by the carcinogen N-hydroxy-1-naphtylamine. Cancer Res 38: 3628–3638
Kimpal RF (1977) The mutagenicity of hydrazine and some of its derivatives. Mutat Res 39: 111–126
Lawley PD (1976) Carcinogenesis by alkylation agents. In: Searle CE (ed) Chemical carcinogens. American Chemical Society Monograph 173, Washington, DC, p 83
Loveless H (1969) Possible relevance of 0–6 alkylation of deoxyguanosine to the mutagenicity and carcinogenicity of nitrosamines and nitrosamides. Nature 223: 206–207
NIOSH Criteria for a recommended standard (1978) Occupational exposure to glycidyl ethers, US Department of Health, Education, and Welfare, National Institute for Occupational Safety and Health, Cincinnati, Ohio, p 197
Nishioka H, Ohtani H (1978) Mutagenicity of epoxide resins; constituents and commercial adhesives. Bacterial test systems. Mutat Res 54: 247–248
Sarma DSR, Rajalakshmi R, Farber E (1975) Chemical carcinogenesis: interactions of carcinogens with nucleic acids. In: Becker FF (ed) Cancer: a comprehensive treatise, vol 1. Plenum Press, New York, p 235
Rannug U, Beije B (1979) The mutagenic effect of 1,2-dichloroethane on Salmonella typhimurium. II. Activation by the isolated perfused rat liver. Chem Biol Interact 24: 265–285
Shugar D, Huber GP, Birnbaum GI (1976) Mechanism of hydroxylamine mutagenesis. Crystal structure and conformation of 1,5-dimethyl-N4-hydroxycytosine. Biochim Biophys Acta 447: 274–284
Singer B (1975) The chemical effects of nucleic acid alkylation and their relation to mutagenesis and carcinogenesis. In: Cohen WE (ed), Progress in nucleic acid research and molecular biology, vol 15. Academic Press, New York, p 219
Singer B (1976) All oxygens in nucleic acids react with carcinogenic ethylating agents. Nature 264: 333–339
Velemínský J, Osterman-Golkar S, Ehrenberg L (1970) Reaction rates and biological action of N-methyl- and N-ethyl-N-nitrosourea. Mutat Res 10: 169–174
Wade DR, Airy SC, Sinsheimer JE (1978) Mutagenicity of aliphatic epoxides. Mutat Res 58: 217–223
Wade MJ, Moyer JW, Hine CH (1979) Mutagenic action of a series of epoxides. Mutat Res 66: 367–371
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Hemminki, K., Falck, K. & Vainio, H. Comparison of alkylation rates and mutagenicity of directly acting industrial and laboratory chemicals. Arch Toxicol 46, 277–285 (1980). https://doi.org/10.1007/BF00310445
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00310445