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Low Levels of Chromosomal Mutations in Germ Cells Derived from Doxorubicin-treated Stem Spermatogonia in the Mouse¹

Departments of Experimental Radiotherapy [M. L. M., M. E. A. B. v. B., S. L. J., J. L.] and Laboratory Medicine [J. C. L.], The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030

The mutagenic effects of doxorubicin (Adriamycin, ADR) on mouse spermatogonial stem cells were examined by analysis of spermatocyte chromosomes and of dominant lethality transmitted through the spermatozoa. The effects of ADR on mutations, cytotoxicity, and sperm head abnormalities were compared with those of radiation. The cytotoxic effect of 6 Gy of -radiation on stem spermatogonia was equivalent to about 4–5 mg ADR/kg. Chromosomal translocations were observed in 0.6% of the spermatocytes of mice treated with ADR (2–6 mg/kg). In contrast, 6 Gy of radiation induced translocations in 11.1% of spermatocytes. No increase in dominant lethality was observed after treatment with ADR at doses up to 6 mg/kg, while the frequency after 6 Gy of radiation was 3.6%. Based on these results, ADR would be expected to be only a weak inducer of balanced chromosomal rearrangements. Because ADR at 4.5 mg/kg was much weaker than 6 Gy of -radiation at inducing chromosomal translocations, but just as effective at inducing sperm head abnormalities, the level of sperm head abnormalities is not indicative of balanced chromosomal rearrangements induced in stem spermatogonia by cytotoxic agents.

¹ Support of this research was provided by Grants CA-17364 (M. L. M.) and CA-43585 (J. C. L.) from the National Institutes of Health.

² To whom requests for reprints should be addressed, at the Department of Experimental Radiotherapy, Box 66, M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030.

Received 7/ 5/89. Revised 10/ 2/89. Accepted 10/16/89.

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