Abstract
The carcinogenicity and mutagenicity of various chromium compounds have been found to be markedly dependent on the oxidation state of the metal. The carcinogen chromate was reduced to chromium(III) by rat liver microsomes in vitro. Metabolism of chromate by microsomal enzymes occurred only in the presence of either NADPH or NADH as cofactor. The chromium(III) generated upon metabolism formed a complex with the NADP+ cofactor. Significant binding of chromium to DNA occurred only when chromate was incubated in the presence of microsomes and NADPH. Specific inhibitors of the mixed function oxidase enzymes, 2′-AMP, metyrapone, and carbon monoxide, inhibited the rate of reduction of chromate by microsomes and NADPH. The possible relationship of metabolism of chromate and its interaction with nucleic acids to its carcinogenicity and mutagenicity is discussed.
Similar content being viewed by others
References
NIOSH,Criteria for a Recommended Standard: Occupational Exposure to Chromium(VI), USDHEW, Public Health Service Center for Disease Control, 1975.
National Research Council, Committee on Biologic Effects of Atmospheric Pollutants,Chromium, Washington, D.C., National Academy of Sciences, 1974.
P. E. Enterline,J. Occup. Med. 16, 523 (1974).
A. Hedenstedt, D. Jenssen, B.-M. Lidesten, C. Ramel, U. Rannug, and R. M. Stern,Scand. J. Work Environ. Health 3, 203 (1977).
A. M. Baetjer,Arch. Ind. Hyg. Occup. Med. 2, 487 (1950).
S. Langard and T. Norseth,Br. J. Ind. Med. 32, 62 (1975).
F. W. Sunderman, Jr.,Food Cosmet. Toxicol. 9, 105 (1971).
A. Furst, M. Schlauder, and D. P. Sasmore,Cancer Res. 36, 1779 (1976).
M. Kuschner and S. Laskin, inMorphology of Experimental Respiratory Carcinogenesis, P. Nettsheim, M. G. Hanna, and J. W. Deatherage, eds., USAEC, Office of Information Services, Washington, D.C., pp. 203–225 (1970).
B. P. Lane and M. J. Mass,Cancer Res. 37, 1476 (1977).
G. D. Stoner, M. B. Shimkin, M. C. Troxell, T. L. Thompson, and L. S. Terry,Cancer Res. 36, 1744 (1976).
P. Nettesheim, M. G. Hanna, D. G. Doherty, R. F. Newell, and A. Hellman, inMorphology of Experimental Respiratory Carcinogenesis, P. Nettsheim, M. G. Hanna, and J. W. Deatherage, eds., USAEC, Office of Information Services, Washington, D.C., pp. 437–448 (1970).
S. Laskin, M. Kuschner, and R. T. Drew, inInhalation Carcinogenesis, M. G. Hanna, P. Nettsheim, and J. R. Gilbert, eds., USAEC, Office of Information Services, Washington, D.C., pp. 321–350 (1970).
S. Venitt and L. S. Levy,Nature 250, 493 (1974).
H. Nishioka,Mut. Res. 31, 185 (1975).
F. L. Petrilli and S. De Flora,Appl. Environ. Microbiol. 33, 805 (1977).
G. Löfroth and B. N. Ames,Mut. Res. 53, 65 (1978).
G. Löfroth,Naturwiss. 65, S207 (1978).
S. Bonatti, M. Meini, and A. Abbondandolo,Mut. Res. 38, 147 (1976).
A. Theodotou, R. J. Stretton, A. H. Norbury, and A. G. Massey,Bioinorg. Chem. 5, 235 (1976).
A. Fradkin, A. Janoff, B. P. Lane, and M. Kuschner,Cancer Res. 35, 1058 (1975).
G. Raffetto, S. Parodi, C. Parodi, M. De Ferrari, R. Troiano, and G. Brambilla,Tumori 63, 503 (1977).
A. G. Levis, M. Buttignol, V. Bianchi, and G. Sponza,Cancer Res. 38, 110 (1978).
M. Miyaki, I. Murata, M. Osabe, and T. Ono,Biochem. Biophys. Res. Commun. 77, 854 (1977).
M. A. Sirover and L. A. Loeb,Science 194, 1434 (1976).
S. J. Gray and K. Sterling,J. Clin. Invest. 29, 1604 (1950).
P. C. Rajam, and A.-L. Jackson,Proc. Soc. Exp. Biol. Med. 99, 210 (1958).
C. J. Sanderson,Transplant. 21, 526 (1976).
P. K. Johnson and M. R. Mardiney,Transplant. 14, 253 (1972).
P. L. Gutierrez, T. Sarna, and H. M. Swartz,Phys. Med. Biol 21, 949 (1976).
H. Herrmann, and L. B. Speck,Science 119, 221 (1954).
S. Eisinger, R. G. Shulman, and B. M. Szymanski,J. Chem. Phys. 36, 1721 (1962).
W. M. Walsh, L. W. Rupp, and B. J. Wyluda,Proc. Intern. Conf. Paramagnetic Resonance 2, 836 (1963).
J. W. Huff, K. S. Sastry, M. P. Gordon, and W. E. C. Wacker,Biochemistry 3, 501 (1964).
A. Danchin,Biochimie 57, 875 (1975).
A. Kowalsky,J. Biol. Chem 244, 6619 (1969).
H. A. Pearson,Blood 22, 218 (1963).
A. M. Baetjer, C. M. Damron, J. H. Clark, and V. Budacz,Arch. Ind. Health 12, 258 (1955).
M. L. De Phamphilis, and W. W. Cleland,Biochemistry 12, 3714 (1973).
J. E. Gruber, and K. W. Jennette,Biochem. Biophys. Res. Commun. 82, 700 (1978).
E. F. Neufield, N. O. Kaplan, and S. P. Colowick,Biochem. Biophys. Acta 17, 525 (1955).
J. Garcia and K. W. Jennette, unpublished results.
A. G. Hildebrandt,Biochem. Soc. Symp. 34, 79 (1972).
Y. Imai and R. Sato,Biochem. Biophys. Res. Commun 22, 620 (1966).
D. A. Haugen, and M. J. Coon,J. Biol. Chem. 251, 7929 (1976).
K. W. Jennette, unpublished results.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Jennette, K.W. Chromate metabolism in liver microsomes. Biol Trace Elem Res 1, 55–62 (1979). https://doi.org/10.1007/BF02783843
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02783843