Sister chromatid exchange induction and the course of DNA duplication, two mechanisms of sister chromatid exchange induction by ENU and the role of BrdU.

Abstract

The aims of the present study were to establish the following: (i) the course of sister chromatid exchange (SCE) induction by ethylnitrosourea (ENU) in the first, second and third divisions as a function of the exposure time; (ii) the persistence of SCE-inducing lesions and the determination of whether or not they are always involved in SCE formation; (iii) the effect of bromodeoxyuridine (BrdU) incorporation on the induction and persistence of SCE. Three-way differential staining of sister chromatids in murine bone marrow cells in vivo was used in the present study. The results indicate the following: (i) SCE induction in each cell division depends on the course of DNA duplication, suggesting that SCE occurs at the replication fork; (ii) the cell population under study could be considered synchronous and had a cell cycle duration of nearly 9 h; (iii) in the second and third cell divisions ENU preferentially induced SCE in the cycle in which the exposure occurred; (iv) lesions induced by exposure to ENU did not cause SCE at the same site in subsequent divisions; (v) ENU was also capable of producing a long-lasting induction of SCE in BrdU-unsubstituted DNA; (vi) the sensitivity to SCE induction by the mutagen increases nearly proportionally to BrdU incorporation into DNA.