Multicellular in vivo sister-chromatid exchanges induced by urethane

Following urethane inhalation exposure, clear dose--response relationships were apparent in all cell types examined in hepatectomized and intact mice. At concentrations of 0.1 mg/l and higher, induced SCE frequencies were linearly related to log urethane concentrations. No significant differences in SCE response between like cell types of hepatectomized and intact mice were apparent. In hepatectomized mice, there was no significant difference in the SCE response of regenerating liver and alveolar macrophage cells. However, bone-marrow response was significantly lower (p = 0.01). Likewise, in intact mice bone marrow response was significantly lower than in alveolar macrophages (p = 0.01). Inhalation and intravenous infusions of the same total dose of urethane (193 mg/kg) administered over a 4-h period produced comparable SCE responses in all cell types. However, a single intraperitoneal injection of 193 mg/kg just prior to BrdU infusion produced significantly higher SCE frequencies in bone marrow (alpha = 0.01), and alveolar macrophages (alpha = 0.05) of intact mice than did the equivalent inhalation dose. Intraperitoneal injections produced similar results in 2-month-old mice as in 4-month-old mice. However, regardless of the route of administration SCE frequencies in regenerating liver and/or alveolar macrophages were significantly higher than in bone marrow.