Induction of Gene Amplification by Arsenic

• Published in: Science (American Association for the Advancement of Science) Vol. 241; no. 4861; pp. 79 - 81
• Main Authors: Lee, Te-Chang, Tanaka, Noriho, Lamb, Patricia W., Gilmer, Tona M., Barrett, J. Carl
• Format: Journal Article
• Language: English
• Published: Washington, DC The American Association for the Advancement of Science 01-07-1988; American Association for the Advancement of Science
• Subjects: Animals; Arsenates; Arsenates - pharmacology; Arsenic; Arsenic - pharmacology; Arsenites; Biological and medical sciences; Bones; Cancer; Carcinogenesis, carcinogens and anticarcinogens; Carcinogens; Cell Line; Cell lines; Cell transformation; Chemical agents; Chromosome replication; DNA - genetics; Drug Resistance; Embryonic cells; Estrogens; Gene amplification; Gene Amplification - drug effects; Genetic aspects; Humans; Medical sciences; Methotrexate; Mice; Neoplasms, Experimental - chemically induced; Neoplasms, Experimental - genetics; Nucleic Acid Hybridization; Oncogenes; Physiological aspects; Poisons & poisoning; Sodium; Sodium Compounds; Tetrahydrofolate Dehydrogenase - genetics; Tumors; Sodium Arsenates; Carcinogen; Gene amplification; Arsenic; Sodium Arsenites; Toxicity; Tetrahydrofolate dehydrogenase; Tumorigenicity
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.3388020

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 longterm animal studies and suggests that these experiments may not detect some environmental agents that act late in the carcinogenic process in humans.