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 in doses of 20, 40 and 80 mg/kg body wt. to ICR mice an dto 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.