Induction of microchromosomes by chemical carcinogens correlates with SV40-DNA amplification in SV40-transformed Chinese hamster cells

Abstract

Radiations and chemical carcinogens induce the amplification of viral DNA inserts and of their cellular flanking sequences in SV40-transformed Chinese hamster embyro cells. In the cell line CO60, the phenomenon is easily measured by in situ hybridization using SV40-DNA as a probe. We found that the appearance of microchromosomes (MC) in CO60 metaphases correlated well with the induction of SV40-DNA amplification (SDA) mediated in the same cells by chemical carcinogens. SDA and MC formation had the same inducers and were essentially transient phenomena whose occurrence and disappearance were simultaneous. The banding properties of MC and the respective time courses of induction of chromosome aberrations and MC formation/disappearance indicated that MC were not chromosome or chromatid breaks but rather acentric double minute-like chromosomes. Double minute chromosomes (DM) have been shown to contain amplified genes. They specifically occur in established cell lines and in vivo tumor cells. Therefore, the reported correlations between SDA and MC formation and the homologies between MC and DM in CO60 cells further support the existence of specific relationships between mutagenesis, gene amplification, in vivo selective pressures and tumor cytogenetics.