Individual susceptibility to DNA telomerase inhibitors: a study on the nuclear damage induced by 3'- azido- 2',3' -dideoxythimidine in lymphocytes from mono- and dizygote aging twins

The activation of telomerase in phytohemagglutinin-stimulated peripheral lymphocytes is thought to play a role in telomere maintenance and DNA repair. Considering the importance of this enzyme in both cancer and senescence, we studied the effects of the telomerase inhibitor 3¢-azido- 3¢-deoxythymidine on the frequency of chromosomal aberrations and micronuclei induced in peripheral blood lymphocytes (PBL) of elderly monozygotic and dizygotic twins, evaluated with respect to the genotoxic effects induced in unrelated young subjects. Our results show that the cytogenetic damage induced by 3¢-azido-3¢-deoxythymidine in human PBL was mainly regulated by genetic factors and allowed the identi®cation of hypersensitive subjects. Ageing, which did not modify the individual susceptibility to 3¢-azido-3¢-deoxythymidine induction of chromosome aberrations and micronuclei, nevertheless determined an overall increase in nuclear damage.