Spermatic toxicity of diazoacetyl-glycine amide (DGA) in mice

Abstract

Summary Female Swiss albino mice were mated with males previously treated with DGA. Whereas a dose of 500 mg/kg/day for 4. days had no appreciable effect, the treatment of the males with 700 mg/kg/ day for 4 days caused a decrease in the number of litters and newborns. DGA is a derivative of diazoacetyl-glycine, with the following chemical structure: N N CH CO NH CH2 CO NH2 It has a marked antitumour activity on the ascitic forms of Sarcoma 180 and Ehrlich carcinoma and on the Galliera rat sarcoma, and a more limited tumour-inhibiting activity on the solid forms of Sarcoma 180 and Ehrlich carcinoma, and on the Harding-Passey melanoma ( Baldini and Brambilla, 1966 ). It also has a remarkable immunodepressant activity. Treatments with DGA significantly prolong the mean survival time of skin graft in H-2 incompatible mice and are effective in allowing the growth of L1210 Leukemia allgrafts in the C$7BL/6 strain and the development of Ehrlich ascites carcinoma in immunized mice ( Brambilla et al., 1970 ). The diazoacetyl-glycine derivatives have a noteworthy toxic activity on many rapidly growing cells and tissues. When administered to animals, they cause bone hypoplasia, marked lymphocytopenia, damage to the gastric and intestinal epithelium, but fail to inhibit rat liver regeneration ( Brambilla et al., 1969 ). The aim of the present investigation was to examine the possible toxic action of DGA on spermatogenesis, which requires synthesis of proteins and nucleic acids, a potential target for the action of DGA.