Adriamycin induces large deletions as a major type of mutation in CHO cells.
Adriamycin (ADR), a commonly used cancer chemotherapy antibiotic, exhibits a variety of genotoxicities. In this study, we have examined the mutagenicity of ADR at the hypoxanthine-guanine phosphoribosyltransferase gene (hprt) in Chinese hamster ovary (CHO) cells and the xanthine-guanine phosphoribosyltransferase locus (gpt) in a pSV2gpt-transformed CHO cell line, AS52. Although ADR induced a dose-dependent increase of mutant frequency at both loci, it was more mutagenic to the gpt gene than to the hprt locus. Multiplex PCR analysis revealed that 35% of the 103 independent ADR-induced HPRT-deficient mutants carried large deletions. Among these deletion mutants, 33% were total gene deletions, 22% affected multiple exons, and 42% involved a single exon, of which most (9/15) were exon 1. The majority (63%) of ADR-induced AS52 mutants had a total deletion of the gpt gene. These observations indicate that ADR induces large deletions as a major type of gene mutation in mammalian cells, suggesting the involvement of reactive oxygen species as one mutagenic pathway in the mutagenesis of ADR.
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Department of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston 77555.
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Hsie
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D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D006224:Cricetinae; D004317:Doxorubicin / Q000633:toxicity*; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D017384:Sequence Deletion
D004317:Doxorubicin; D007041:Hypoxanthine Phosphoribosyltransferase