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

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Abstract
Heliotrine causes an almost complete suppression of cell division in leukocyte cultures at a concentration of 2 x 10-4[image]; below 1 x 10-6[image], its effect on the mitotic index is very slight. The mean interval for cells to enter 1st mitosis is extended by 10 hr. with 5 x 10-5[image] heliotrine. Both chromosome and chromatid breaks are produced at this latter concentration of heliotrine, the total damage being approximately equivalent to that produced by 300 r of X-irradiation delivered at 25 r/min. The chromosome breakage is considered to be true chromosome damage since it appears in cells in 1st 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 of heliotrine is compared. The distribution of damage by heliotrine and X-irradiation shows a non-random pattern. The overdispersion is marked in heliotrine treatments. This pattern is related to the distribution of heterochromatin.