The kinetics of nuclear polyploidization and tumour formation in livers of CF-1 mice exposed to dieldrin.

The kinetics of nuclear polyploidization in livers of CF-1 mice exposed to dieldrin were studied at concentrations of 0, 0.1, 1, 5 and 10 p.p.m. in the diet, in 'steady-state' situations (which are reached within a few weeks after initiation of treatment). Animals were killed at five time intervals (after 1.85, 3, 6, 9 and 14 months of exposure). The changes in the percentage of octaploid nuclei (8C) were used as an indicator of the kinetics of overall polyploidization. Polyploidization in control mice increased proportionally (linearly) with time (age). The enhancement of polyploidization by dieldrin was found to be proportional to dietary concentration. The slopes of the linear regressions of polyploidization, as a function of age, were identical in all dieldrin-treated groups and controls, indicating that there was no cumulative effect of dieldrin in time. A comparative analysis of the observed dieldrin dietary concentration: response relationship of polyploidization and of tumour formation in CF-1 mouse liver indicates that liver tumour formation is associated with a constant degree of polyploidization. Assuming that polyploidization reflects the ageing process, the data suggest that liver tumour formation is imminent at a constant biological age and that tumour promoters, such as dieldrin, could operate by advancing the biological age of mouse liver in the initial phases of treatment. The results of this study suggest that the analysis of ploidy changes may serve as an aid to perspective in evaluating risks associated with exposures to liver tumour promoters.