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Science 1 July 1988:
Vol. 241. no. 4861, pp. 79 - 81
DOI: 10.1126/science.3388020
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Articles
Science, Vol 241, Issue 4861, 79-81
Copyright © 1988 by American Association for the Advancement of Science
Induction of gene amplification by arsenic
TC Lee,
N Tanaka,
PW Lamb,
TM Gilmer,
and
JC Barrett
Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Arsenic is a well-established carcinogen in humans, but there is little evidence for its carcinogenicity in animals and it is inactive as an initiator or tumor promoter in two-stage models of carcinogenicity in mice. Two arsenic salts (sodium arsenite and sodium arsenate) induced a high frequency of methotrexate-resistant 3T6 cells, which were shown to have amplified copies of the dihydrofolate reductase gene. The ability of arsenic to induce gene amplification may relate to its carcinogenic effects in humans since amplification of oncogenes is observed in many human tumors. The inability of arsenic to induce gene mutations may relate to the negative results of arsenic in long-term animal studies and suggests that these experiments may not detect some environmental agents that act late in the carcinogenic process in humans.
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