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Damaging Effects of Fourteen Chemotherapeutic Drugs on Mouse Testis Cells¹

Department of Experimental Radiotherapy and Cell Biology, The University of Texas System Cancer Center, M. D. Anderson Hospital and Tumor Institute, Houston, Texas 77030

The harmful effects of 14 chemotherapeutic drugs on spermatogenesis in the mouse have been evaluated by studies of testicular cell killing and morphological and genetic damage produced. Male mice were given drugs as single injections at various doses up to the toxic levels. Prednisone and 6-mercaptopurine produced little or no cytotoxicity. All other drugs tested killed differentiated spermatogonia. Of these, methotrexate, cyclohexylchlorethylnitrosourea, cis-platinum, and mechlorethamine did not show significant stem cell killing. Bischlorethylnitrosourea, chlorambucil, 5-fluorouracil, mitomycin C, actinomycin D, and procarbazine showed some stem cell killing. Triethylenethiophosphoramide (thio-TEPA) was the only drug in this group which killed large numbers of stem cells. Only 5-fluorouracil and cis-platinum killed spermatocytes, and only cis-platinum killed spermatids. Several drugs induced chromosome breaks in treated spermatocytes. Thio-TEPA was effective in inducing chromosome translocations in treated spermatocytes and probably also in spermatocytes which originated from surviving treated stem cells.

It had been our hypothesis that the cytotoxic effects of these drugs on mouse testicular stem cells would correlate with the duration of azoospermia observed in patients. This was shown not to be the case. Thus, the cytotoxic effects of single injections of single chemotherapeutic agents on the mouse testis did not appear to be predictive of which drugs will cause long-term azoospermia in humans.

¹ This investigation was supported by Grants CA-17364 and CA-06294, awarded by the National Cancer Institute. Department of Health, Education, and Welfare. Animals used in this study were maintained in facilities approved by the American Association for Accreditation of Laboratory Animal Care and in accordance with current regulations and standards of the United States Department of Health, Education, and Welfare, NIH.

² Present address: Fachklinik Hornheide, Universitaet Muenster, Muenster, West Germany.

³ Present address: Biology Division, Oak Ridge National Laboratory, P. O. Box Y, Oak Ridge, Tenn. 37830.

Received 4/29/81. Accepted 9/10/81.

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