ADAPTIVE AND SYNERGISTIC EFFECTS OF A LOW-DOSE ENU PRETREATMENT ON THE FREQUENCY OF CHROMOSOMAL-ABERRATIONS INDUCED BY A CHALLENGE DOSE OF ENU IN HUMAN PERIPHERAL-BLOOD LYMPHOCYTES IN-VITRO

N-Ethyl-N-nitrosourea (ENU) is an alkylating agent whose mutagenic and carcinogenic potential has been extensively studied but its ability t o induce cytogenetic adaptive responses in normal human cells has not been investigated so far. The aim of our present experiments was to st udy the effect of a pretreatment with a low concentration of ENU (2 X 10(-5) M) on the frequency of chromosomal aberrations induced by a sub sequent 50 times higher concentration of ENU (10(-3) M) in human lymph ocytes isolated from buffy coats of 4 donors. Two different inter-trea tment times and three harvesting times were applied to the lymphocytes from each donor. A cytogenetic adaptive response was shown by the lym phocytes of one donor only when the time span between the low adapting and the higher challenging concentration was 4 h, The other three don ors did not respond with significant differences in the yield of cells with aberrations. The complex interaction between the ENU-induced mul tiple primary DNA lesions and various DNA repair mechanisms as well as the influence of cell cycle effects on the induction of clastogenic a daptive response are discussed.