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

Abstract

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