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Induction of sister chromatid exchange by ethyl carbamate and vinyl carbamate
Abstract:
High levels of sister chromatid exchanges (SCEs) can be induced in murine bone marrow, alveolar macrophages and regenerating liver cells by carcinogenic carbamate esters; however, the frequencies observed in the latter two tissues, which are also common tissues for carbamate-induced tumours, are relatively enhanced compared to the frequency in bone marrow. Relative to these tissues, peripheral blood lymphocytes, which do not divide during in-vivo exposure but which can be cultured in vitro, exhibit considerably lower levels of ethyl-carbamate-induced SCEs. Lymphocytes, however, are uniquely able to accumulate SCE-inducing lesions produced by multiple treatments with ethyl carbamate. In the present study, significantly elevated levels of SCEs were still apparent in lymphocytes of BDF1 mice eight weeks after a series of 12 multiple injections (2.2 mmol/kg; 3 times weekly) of ethyl carbamate. Long-term persistence of genetic damage produced by ethyl carbamate in murine lymphocytes is in agreement with our previous findings of highly persistent SCE-inducing damage in murine bone marrow and alveolar macrophage cells. The highly persistent nature of ethyl-carbamate-induced DNA damage and/or its continued ability to induce SCEs is undoubtedly relevant to its tumourigenic activity.