Chlorozotocin, an anti-tumour agent lacking bone marrow toxicity at therapeutic doses: effects on lymphocyte subpopulations in mice

Abstract

Chlorozotocin is a new nitrosourea anti-tumour drug that does not produce bone marrow suppression at therapeutic doses in mice. CDF1 mice which were injected i.p. with a dose lethal to 10% of animals within 60 days (LD10), 20 mg/kg, developed a 50% reduction in circulating peripheral blood lymphocytes without a decrease in circulating granulocytes by day 3. Spleen weight also decreased markedly. The percentage of spleen B and T cells, determined by immunofluorescence with goat anti-mouse IgG and rabbit anti-mouse brain antisera, did not differ in control and chlorozotocin-treated mice. However, the ability of residual spleen cells to proliferate in response to phytohaemagglutinin, concanavalin A, pokeweed mitogen, and allogeneic cells was significantly suppressed although the lipopolysaccharide response was not reduced. The ability of the mice to respond to a primary immunization with sheep red blood cells was not significantly impaired. Therefore, chlorozotocin has a cytotoxic effect on both B and T cells but selectively inhibits the proliferative capacity of T cells. B cell proliferation and B cell function as measured in a primary antibody response were not reduced. These studies suggest chlorozotocin may be useful as an immunosuppressive drug as well as an anti-tumour agent.