title: Persistence of ethyl carbamate-induced DNA damage in vivo as indicated by sister chromatid exchange analysis.
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 X 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.
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D002453:Cell Cycle; D002470:Cell Survival / Q000187:drug effects; D003434:Crossing Over, Genetic; D004247:DNA / Q000032:analysis*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D008433:Mathematics; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D012854:Sister Chromatid Exchange; D014520:Urethane / Q000494:pharmacology*
chemical_list: D014520:Urethane; D004247:DNA