Effects of the Pyrrolizidine Alkaloid Heliotrine on Cell Division and Chromosome Breakage in Cultures of Leucocytes from the Marsupial Potorous Tridactylus

Abstract

Heliotrine causes an almost complete suppression of cell division in leucocyte cultures at a concentration of 2 X 10-4M; below 1 X 10-6M, its effect on the mitotic index is very slight. The mean interval for cells to enter first mitosis is extended by 10 hr with 5 X 1O-5M heliotrine. Both chromosome and chromatid breaks are produced at this latter concentration of heliotrine, the total damage being approxi. mately equivalent to that produced by 300 r of X-irradiation delivered at 25 rJmin. The chromosome breakage is considered to be true chromosome damage since it appears in cells in first division following treatment. Thus it would appear that heliotrine is capable of breaking the chromosomes in G1. i.e. before DNA synthesis. Most alkylating agents do not demonstrate any capacity to induce breakage before the replicating phase. Breakage in G1 has been demonstrated by treatment with hydroxylamine and 8-ethoxycaffeine with which the action ofheliotrine is compared.