Effects of morphine sulphate on the germ cells of male mice

Abstract

The dominant lethal test and the spermatocyte test were used to assess the mutagenic effect of morphine sulphate in male mice. Pregnant females were examined at midterm for the number of corpora lutea and intrauterine contents. The effect of the drug on total embryonic losses was very marked at the 1-, 2-, 3-, and 6-week mating intervals. However, the effect of morphine treatment was much more marked and consistent on preimplantation deaths than on early deaths. The consistently high mutation indices (MI) obtained in different treatment groups implied that morphine specifically affected the early spermatid stage (MI 30, 46, 77, and 31 for the groups treated with 10, 20, 40, and 60 mg morphine, respectively). High mutation indices in the range of 20–36 were shown by a few other spermatogenic stages but were not systematically exhibited by all groups. The spermatocytes of a second group of treated males were examined 45–50 days after treatment with either morphine or saline. The cytogenetic analysis of spermatocytes at diakinesis-metaphase 1 showed significant increases in the frequency of multivalent configuration, translocation, and autosomal and sex chromosome univalents in the groups treated with morphine, compared with the spontaneous rates of the control group. In general, the different doses of morphine resulted in a total chromosomal aberration frequency of approximately 3–6 times the control value, demonstrating nearly a linear dose-response relationship. The results obtained from both test systems in the mouse suggest that morphine in the doses given is potentially mutagenic in this species and can induce sustained chromosomal aberrations in premeiotic stages.