Measurement of DNA damage by the comet assay in rat embryos grown in media containing high concentrations of vitamin K(1)

Abstract

It has been suggested that vitamin K(1) (phylloquinone) can cause genetic damage in rapidly dividing cells and that this should be considered in the risk/benefit analysis of the prophylactic use of vitamin K(1) in the newborn. Usual intramuscular administration of 1mg of vitamin K(1) to the newborn gives peak plasma levels of 1-2 microg/ml (approximately 2-4 microM). To investigate the possible harmful effects of high concentrations of vitamin K(1), rat embryos undergoing rapid cell division in the organogenic period were cultured for 46 hours in rat sera containing either 1, 10 or 100 microg of added vitamin K(1) per ml (2, 22 or 222 microM). At the end of the culture period the embryos were dissociated and the cells examined for evidence of DNA damage using the alkaline version of the comet assay. Control embryos were cultured in sera without added vitamin K(1) and positive controls were control embryos exposed to hydrogen peroxide at the end of the culture period. The results did not show any evidence of DNA damage in the vitamin K(1) exposed embryos. The positive controls showed a significant increase in tail length, moment and inertia. In conclusion, under the experimental conditions used, high concentrations of vitamin K(1) did not induce primary DNA damage in cells from rat embryos grown in vitro.