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Long-Term Persistence of Ethyl Carbamate-induced Sister Chromatid Exchanges in Murine Lymphocytes¹

Departments of Industrial Environmental Health Sciences [M. K. C., T. T.] and Biostatistics [R. E. N., M. K. C.], Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15261

Ethyl carbamate-induced sister chromatid exchange (SCE) was evaluated at 20 min and 1, 3, 4.5, 5.5, 7, and 9 h postexposure (acute dose, ethyl carbamate, 3.3 mmol/kg) in concanavalin A (Con A)- and lipopolysaccharide (LPS)-stimulated murine peripheral blood lymphocytes (PBL). In both Con A- and LPS-stimulated PBL, SCE responses peaked between 4.5 and 5.5 h postinjection, a time which corresponds to complete biotransformation of ethyl carbamate. Peak induced SCEs for Con A- and LPS-stimulated PBL were 6.43 and 7.44, respectively.

SCE responses were also evaluated in Con A- and LPS-stimulated PBL at 3 and 24 h following the last of a series of two, four, or six i.p. injections of ethyl carbamate (3.3 mmol/kg) given every other day. Dose-related increases (presumably reflecting the accumulation of unrepaired SCE-inducing damage) in SCEs were observed at both times following two and four injections of ethyl carbamate. However, following six injections a decrease in SCE response and increased cytotoxicity were observed.

Persistence of SCE-inducing DNA lesions was observed in blood, spleen, and parathymic node lymphocytes following the last of a series of 12 i.p. injections (three times weekly) of ethyl carbamate (2.2 mmol/kg). With the exception of LPS-stimulated blood lymphocytes, exposed blood and spleen Con A- and LPS-stimulated lymphocyte populations contained a significantly higher number of high-frequency cells than did their respective controls at 16 weeks postexposure. The gradual return of SCE levels to base-line values appears to be primarily a consequence of slow population turnover. Parathymic node lymphocytes exhibited elevated SCE responses (2 times base-line levels) for up to 4 weeks postexposure.

¹ This study was supported by National Institute of Environmental Health Sciences Grant 1 R01 CA 33869-01.

² To whom requests for reprints should be addressed.

³ Present address: Department of Health Sciences, Yamanashi Medical College, Tamaho, Nakakoma, Yamanashi, Japan.

Received 3/13/85. Revised 5/23/85. Accepted 5/31/85.