Chromosome-breaking capacity of tepa and analogues in Vicia faba and Chinese hamster cells

Abstract

The insect chemosterilant tris(l-aziridinyl)phosphine oxide, tepa, with three aziridinyl groups, six tepa analogues with two aziridinyl groups and carbon chains of varying length, one monoaziridinyl analogue of tepa, and hempa with no aziridinyl group have been tested for chromosome-breaking ability in root tips of Vicia faba and in cell cultures of Chinese hamster. The difunctional analogues proved to be as active as tepa in both materials; the monofunctional analogue was less effective and hempa produced no effect. The hamster cells proved to be 23 times more sensitive than the bean roots to the chromosome-breaking effect of tepa. In the hamster cells the chromatid break was the most frequent type of aberration. Incomplete chromosomal aberrations were more numerous in the hamster cells than in the root tips. Combined treatments with tepa and [3H]-thymidine were performed to determine the sensitivity of the various phases of the mitotic cycle to the chromosome-breaking effect in the two materials. Treatment with tepa induced only chromatid-type aberrations. Chromosomal aberrations at the first mitosis (T1) were observed only in cells treated with tepa while in the DNA synthesis (S) and pre-synthetic (G1) periods, but not in the post-synthetic (G2) period. In the second mitosis (T2), G2 cells which were visibly undamaged at T1 mitosis, contained chromatid-type aberrations. The frequency of aberrations observed in T2 mitosis was higher than in T1 mitosis. Thus, although tepa produces lesions in chromosomes independently of cell phase at the time of treatment, these lesions apparently require a period of DNA synthesis before they are converted to chromatid aberrations observable in the following mitosis.