RELATION BETWEEN RATE OF CELL-PROLIFERATION AND FORMATION OF MICRONUCLEI AFTER COMBINED TREATMENT WITH X-RAYS AND CAFFEINE

We studied the effects of caffeine (2 mm), X-rays (1 Gy) and the combi nation of both agents on cell proliferation and formation of micronucl ei in the early stages of preimplantation mouse embryos in vitro. Two- cell embryos were exposed to the agents shortly before division to the 4-cell stage. Proliferation and micronucleus production was monitored every 2 h in the 4- and 8-cell stages. A rather peculiar pattern of m icronucleus formation after radiation exposure alone was observed for 8-cell embryos: those embryos that were the first to enter the 8-cell stage showed two to three times higher numbers of micronuclei per cell when compared with those embryos that entered the 8-cell stage some h ours later. Studies of the kinetics of cell proliferation and of micro nucleus formation in 4- and 8-cell embryos and exposure to caffeine re vealed that this result could be explained by two factors: a slight as ynchrony in the developmental stage at the time of exposure and the le ngth of the interval being available for repair processes. When caffei ne was present, a third factor had to be taken into consideration: dir ect inhibition of repair by caffeine.