The genotoxic effects of adriamycin in somatic and germinal cells of the mouse.

The genotoxic effects of adriamycin on somatic and germinal cells were studied in mice treated with single injections of 3, 12 or 24 mg/kg of the drug. From 1 to 5 days post-injection, chromosome aberrations were observed in bone-marrow cells and in diakineses-metaphase I cells from the testes. The frequency of chromosome breakages peaked at 5 h or 1 day for the bone marrow and at 3 and 5 days for the testis. Univalent formation was increased overall but did not have a dose- and time-dependent relationship. In long-term follow-up studies, adriamycin was found to induce cell killing of germline cells which resulted in a reduction in the numbers of spermatocytes and sperm from mice treated with the higher doses. There was complete absence of gametogenetic elements and, eventually, testicular atrophy occurred. In mice treated with 3 mg/kg, there was gradual recovery of spermatogenesis from 50 days onward. Chromosome breaks and translocations were again observed in the recovering spermatocytes. It was concluded that some of the chromosome aberrations must have been induced in the spermatogonial cells which had survived.