Relationship between experimental results in mammals and man. II. Cytogenetic analysis of bone-marrow cells after treatment of cytembena and cyclophosphamide- cytembena combination

Abstract

Cytogenetic analysis and the micronucleus test of bone-marrow cells was used to study the possible extrapolation of results from experimental animals to man. Cytembena was given i.p. in doses of 5, 10, 20, 40 and 80 mg/kg body wt. to Wistar rats and in doses of 20, 40 and 80 mg/kg body wt. to ICR mice and to Chinese hamsters. Five patients with various types of malignancy, so far medically untreated, received 20 mg Cytembena/kg body wt i.v. A combination of Cytembena and cylophosphamide was applied i.p. in single equal doses 1 : 1 of 5,10, 20, and 40 mg/kg body wt to ICR mice, Chinese hamsters and Wistar rats. Patients were given i.v. 20 mg Cytembena and 20 mg cyclophosphamide/kg body wt. Bone-marrow cells were examined 24 h after the administration. The frequency of abnormal metaphases and chromosomal breaks after Cytembena treatment was low; nonetheless, the indicated dose-effect relationship was found in all the rodents used. The frequency of chromosomal breaks was 2--3 times higher in rodents in comparison with man, after treatment with a dose of 20 mg Cytembena/kg body wt. Highest frequencies of induced aberrations were found in mice. The rodents appeared to be 3--4 times more sensitive to the induction of chromosomal breaks and abnormal metaphases than man, after a dose of 20 mg Cytembena and 20 mg cyclophosphamide/kg body wt. The micronucleus test may be regarded as a screening method for assessing mutagenic activity of chemical compounds. Chromosomal analysis and the micronucleus test were about equally convincing in detecting mutagenic effects even with the lowest doses of drugs used. However, the dose-effect relationship was more pronounced in chromosomal aberrations than in the micronucleus test.