Immunotoxic potential of N-ethyl, N-nitrosourea (ENU) in CD1 mice

The immunotoxic potential of ENU, a potent and transplacental neurocarcinogen, was evaluated in male CD1 mice. The animals received i.p. injections of ENU--0, 2, 8 or 32 mg/kg body weight, in citrate-phosphate buffer, twice weekly for three weeks. Splenic lymphocytes were cultured in the presence of mitogens, lipopolysaccharide, pokeweed mitogen, concanavalin A and phytohaemagglutinin. Mixed lymphocyte cultures in the presence of allogeneic cells were also tested. Blastogenic response decreased in a dose-dependent manner, as measured by the 3H-thymidine uptake by splenocytes. Primary antibody production by splenic lymphocytes from animals challenged with a T-dependent antigen (sheep red blood cells) was stimulated at low doses but depressed at the highest dose group compared with the controls, whereas T-independent cell response showed no significant change. Our results suggest that exposure to repeated, low levels of ENU significantly alters the immune status of CD1 mice. The effects appear to be somewhat selective to T cell processes, based on in vivo responses to T-dependent and T-independent antigens.