ABSTRACT
This chapter describes results on arsenic-induced gene amplification and discusses the possible mechanisms for this effect. This is the same relative potency of the two compounds in cell transformation assays, and the dose-response results for induction of gene amplification and cell transformation are similar. The mechanism by which arsenic induces gene amplification remains unknown, although several possibilities can be considered. Therefore, arsenic-induced gene amplification is unlikely to be due to direct DNA base damage. Gene amplification has been hypothesized to arise either by a recombinational mechanism or by inhibition of DNA synthesis and overreplication. Asymmetric segregation of chromosome fragments or unequal sister chromatid exchange is one possible explanation for the mechanism of gene amplification in drug-treated mammalian cells.
