CHARACTERIZATION OF PHENOTYPIC ALTERATIONS INDUCED BY 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN ON THYMOCYTES IN-VIVO AND ITS EFFECT ON APOPTOSIS

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a highly toxic environme ntal pollutant and is well known for inducing thymic atrophy in mice, although the exact mechanism of its action rc:mains unclear. Recent st udies from our laboratory demonstrated that TCDD induces apoptosis in thymocytes and that Fas(-) mice (lpr/lpr) were more resistant to TCDD- induced immunotoxicity when compared to the Fas(+) wild-type mice. Ina smuch as induction of apoptosis is associated with alterations in adhe sion molecule expression, in the current study we analyzed the express ion of a variety of surface molecules on thymocytes treated with TCDD in vivo. Interestingly, in thymocytes from mice treated with a single dose of 50 mu g/kg body wt of TCDD, there was a significant increase i n the density of expression of CD3, alpha beta TCR, CD44, and IL-2R, a nd a decrease in the expression of J11d, CD4, and CD8 molecules when c ompared to the control thymocytes. These alterations were first visibl e 3 da iis after TCDD treatment and increased on Days 5 and 10 posttre atment. Furthermore, most of the alterations in the density of express ion of various markers were dose dependent with minimal but significan t changes at 0.1 mu g and maximum alterations at 50 mu g/kg body wt of TCDD. At most lower concentrations (0.1-5 mu g/kg), TCDD caused alter ations in the density of cell surface markers but not in the percentag e of cells expressing a specific molecule. It is striking that the phe notypic alterations were similar to those seen in normal thymocytes un dergoing spontaneous apoptosis in vitro as previously reported. Togeth er, the current study suggests that TCDD treatment induces phenotypic changes in thymocytes that are similar to those seen in normal thymocy tes undergoing apoptosis, Also, because detection of apoptosis in vivo is difficult, phenotypic alterations in the density of thymocyte surf ace molecules may serve as a useful biomarker for toxicity involving a poptosis. (C) 1998 Academic Press.