Sister chromatid exchange induction in mouse B- and T-lymphocytes exposed to cyclophosphamide in vitro and in vivo

Cyclophosphamide (CPA) is known to exert greater toxic effects of B- than on T-lymphocytes in vivo. Both in vitro and in vivo CPA treatments were used to assess the possible cytogenetic basis for these observations. First, male C57BL/6 mouse lymphocytes were stimulated to divide in vitro with either phytohemagglutinin (T-cell mitogen) or lipopolysaccharide (B-cell mitogen), and were then treated with CPA (0.05 to 1.0 mM) and 5-bromo-2'-deoxyuridine (2 microM) at 24 hr. Cultures were harvested at 60 hr following a 4-hr treatment with demecolcine (1.35 microM). CPA caused concentration-related increases in sister chromatid exchange (SCE) up to 3 times control frequencies; the resulting SCE induction curves for B- and T-cells were sigmoidal and equivalent. Second, mice were given a single i.p. injection of CPA (0.5, 1.0, or 5.0 mg/kg). Blood was removed 24 hr later and cultured without additional CPA, as described above. Dose-related increases in SCE frequencies were seen for both T- and B-lymphocytes. CPA induced consistently 2.5 to 3.7 more SCEs in B-cells than in T-cells. Thus, B- and T-lymphocytes exhibited an equal sensitivity to CPA in vitro, but B-cells were more susceptible to the genotoxic effects in vivo.