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Thymocytes and splenocytes are believed to be used as model systems to investigate T cell development. However, thymocytes and splenocytes are more susceptible to beta-propiolactone (BPL)-induced apoptosis than are other lymphocyte subsets, and the processes that may account for the observed cell-specific sensitivity have not been thoroughly investigated. In this report, we examined the effects of BPL, a nonspecific DNA alkylating agent, on splenocytes and thymocytes from Sprague-Dawley rats. We determined the susceptibility of splenocytes to BPL at different times after i.p. treatment and found that the exposure time effect was biphasic. During the first 3 h after i.p. treatment, splenocyte apoptosis was inversely related to time after treatment and became maximal within 3 h. In contrast, 3 h was not sufficient to induce maximal apoptosis in thymocytes. Consistent with the thymocyte-specific requirement for longer exposure, thymocytes from naive rats were more resistant to BPL compared with those from rats that had undergone 4 weeks of age, suggesting that thymocytes might have undergone some previous exposure to thymus-derived hormones or environmental factors. In addition, because thymocytes also display a biphasic response to 2′,2′-difluorodeoxycytidine
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