Persistence of Ethyl Carbamate-induced DNA Damage in Vivo as Indicated by Sister Chromatid Exchange Analysis

TLDR: Second- and third-division cell SCE data produced by the various protocols indicate persistence of SCE-inducing lesions with no evidence of repair, and first-cycle ethyl carbamate treatment was less effective than was second-cycle treatment in inducing SCEs.

Abstract: Various treatment protocols were designed to investigate sister chromatid exchanges (SCEs) induced over successive posttreatment cell cycles in bone marrow and alveolar macrophage cells following treatment of C57BL/6J × DBA/2J F1 mice by i.p. injection of ethyl carbamate (3.3 mmol/kg). The same initial extent of alkylation in bone marrow and alveolar macrophages was suggested by identical SCE frequencies produced in both cell types by a one-cycle exposure protocol. The relatively lower responses in bone marrow cells by all other protocols may be a result of its faster mean population-cycling time. Second- and third-division cell SCE data produced by the various protocols indicate persistence of SCE-inducing lesions with no evidence of repair. In spite of the demonstrated lack of repair, first-cycle ethyl carbamate treatment was less effective than was second-cycle treatment in inducing SCEs. These results could not be attributed to selection of less-damaged cells over 2 cycles or to enhanced bromodeoxyuridine sensitivity in the second-cycle treatment protocol. It is speculated that the apparent cancellation of SCEs occurring over two successive cycles in the two-cycle exposure protocol may indicate the transient presence of ethyl carbamate-induced DNA interstrand cross-links. A possible mechanism of action of ethyl carbamate involving the formation of a transient cross-link and a persistent DNA monoadduct is postulated.