Abstract
Arsenic compounds are known carcinogens. Although many carcinogens are also mutagens, we have previously shown that sodium arsenite is not mutagenic at either the Na+/K+ ATPase orhprt locus in Chinese hamster V79 cells. It can, however, enhance UV-mutagenesis. We now confirm the nonmutagenicity of sodium arsenite in line G12, a pSV2gpt-transformed V79 (hprt −) cell line, which is able to detect multilocus deletions in addition to point mutations and small deletions. The lack of arsenic mutagenicity has led to studies emphasizing its comutagenicity. Sodium arsenite at relatively nontoxic concentrations (5 μM for 24 h or 10 μM for 3 h) is comutagenic withN-methyl-N-nitrosourea (MMU) at thehprt locus in V79 cells. Using a nick translation assay, which measures DNA strand breaks by incorporating radioactive deoxyribonucleoside monophosphate at their 3′OH ends in permeabilized cells, we found that much more incorporation was seen in cells treated with MNU (4 mM, 15 min) followed by 3-h incubation with 10 μM sodium arsenite compared with cells exposed to the same MNU treatment followed by 3-h incubation without sodium arsenite. This result shows that in the presence of arsenite, strand breaks resulting from MNU or its repair accumulate over a 3-h period. We suggest that the repair of MNU-induced DNA lesions may be inhibited by arsenite either by affecting the incorporation of dNMPs into the MNU-damaged DNA template or by interfering with the ligation step.
Similar content being viewed by others
References
F. W. Sunderman,Biol. Trace Element Res. 1, 63 (1979).
A. Leonard and R. R. Lauwerys,Mutat. Res. 75, 49 (1980).
IARC:Arsenic and inorganic arsenic compounds. Monograph in the evaluation of carcinogenic risk of chemicals to man, vol. II, IARC, Lyon, 1973, pp. 48–73.
IARC:Carcinogenesis of arsenic compounds. IARC monograph on evaluation of carcinogenic risks, vol. 23, IARC, Lyon, 1980, pp. 37–141.
T. G. Rossman, D. Stone, M. Molina, and W. Troll,Environ. Mut. 2, 371 (1980).
G. Lofroth and B. N. Ames,Mutat. Res. 53, 65 (1978).
D. E. Amacher and S. C. Paillet,Mutat. Res. 78, 279 (1980).
F. Bertolero, G. Pozzi, E. Sabbioni, and U. Saffiotti,Carcinogenesis 8, 803 (1987).
T. G. Rossman,Mutat. Res. 91, 207 (1981).
T. C. Lee, R. Y. Huang, and K. Y. Jan,Mutat. Res. 148, 83 (1985).
T. C. Lee, S. Wang-Wuu, R. Y. Huang, K. C. C. Lee, and K. Y. Jan,Cancer Res. 46, 1854 (1986).
G. R. Paton and A. C. Allison,Mutat. Res. 16, 332 (1972).
M. L. Larramendy, N. C. Popescu, and J. A. DiPaolo,Environ. Mut. 3, 597 (1981).
J. A. DiPaolo and B. C. Casto,Cancer Res. 39, 1008 (1979).
T. Okui and Y. Fujiwara,Mutat. Res. 172, 69 (1986).
B. Singer and T. P. Brent,Proc. Natl. Acad. Sci. 78, 856 (1981).
B. Singer,Environ. Health Perspect. 62, 41 (1985).
T. Lindahl,Ann. Rev. Biochem. 51, 61 (1982).
W. Warren, A. R. Crathorn, and K. V. Shooter,Biochim. Biophys. Acta 563, 82 (1979).
R. Goth-Goldstein,Cancer Res. 40, 2623 (1980).
R. S. Foote and S. Mitra,Carcinogenesis 5, 277 (1984).
O. Cantoni and M. Costa,Carcinogenesis 5, 1207 (1984).
R. D. Snyder and D. W. Matheson,Environ. Mut. 7, 267 (1985).
C. B. Klein, PhD Thesis, New York University (1988).
C. C. Chang, M. Castellazzi, T. W. Glover, and J. E. Trosko,Cancer Res. 38, 4527 (1978).
A. Weissbach,Arch. Biochem. Biophys. 198, 386 (1979).
M. R. Miller and D. N. Chinault,J. Biol. Chem. 257, 46 (1982).
M. R. Miller and D. N. Chinault,J. Biol. Chem. 257, 10204 (1982).
D. Creissen and S. Shall,Nature 296, 271 (1982).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Li, J.H., Rossman, T.G. Mechanism of comutagenesis of sodium arsenite withn-methyl-n-nitrosourea. Biol Trace Elem Res 21, 373–381 (1989). https://doi.org/10.1007/BF02917278
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02917278