Dominant lethal effects of nocodazole in germ cells of male mice.

ABSTRACT

The ability of the anticancer drug, nocodazole, to induce dominant lethal mutations in male germ cells was investigated by the in vivo dominant lethal test. Mice were treated with single doses of 15, 30 and 60 mg/kg nocodazole. These males were mated at weekly intervals to virgin females for 6 weeks. Nocodazole clearly induced dominant lethal mutations in the early spermatid stage with the highest tested dose. Mice treated with 60 mg/kg nocodazole showed an additional peak of dominant lethal induction in mature spermatozoa during the first week matings after treatment. The percentage sperm count and sperm motility were significantly decreased after treatment of males with 30 and 60 mg/kg nocodazole. Moreover, the middle and highest doses of nocodazole significantly increased the percentage of abnormal sperm. Our study provides evidence that nocodazole is a germ cell mutagen. Marked alteration in the spermiogram analysis after nocodazole treatment possibly confirms that nocodazole has a significant effect on sperm maturation and development during storage and transit. The demonstrated mutagenicity profile of nocodazole may support further development of effective chemotherapy with less mutagenicity. Moreover, the cancer patients and medical personnel exposed to this drug chemotherapy may stand a higher risk for abnormal reproductive outcomes.