Effects of N-nitrosodimethylamine on humoral immunity

MP Holsapple, AN Tucker, PJ McNerney and KL White

Female B6C3F1 mice were given i.p. injections with 1.5, 3.0 and 5.0 mg/kg N-nitrosodimethylamine (DMN) daily for 14 days and evaluated on day 15. The day 4 immunoglobulin M (peak day) antibody response to sheep red blood cells (sRBC) was inhibited by 20, 53 and 81%, respectively. The day 5 immunoglobulin G (peak day) antibody response to sRBC was only inhibited significantly (60%) at the highest dose. Recovery studies indicated that the IgM antibody response was still significantly inhibited (48%) 30 days after the completion of the exposure to 5 mg/kg of DMN. The peak response (day 3) to 100 micrograms of the B-cell mitogen, lipopolysaccharide, was inhibited by 15, 26 and 32%, respectively, indicating that a portion of the suppression of the antibody response by DMN may be due to an effect on the ability of the lymphocytes to proliferate. Concentrations of DMN up to 100 mM added directly to untreated spleen cell suspensions had no effect on the in vitro antibody responses to lipopolysaccharide and sRBC. Preincubating DMN (100 mM) with either phenobarbital-induced or 3-methylcholanthrene- induced liver proteins (postmitochondrial supernatant from a 9000 X g liver homogenate) was still ineffective. The activation of DMN by either preparation was verified by measuring formaldehyde production, which reflects demethylation. In contrast to the results with DMN added directly to untreated spleen cell suspensions, the most sensitive indicator of suppression by DMN was the in vitro antibody responses to lipopolysaccharide and sRBC by spleen cell suspensions from DMN-treated mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 229, Issue 2, pp. 493-500, 05/01/1984
Copyright © 1984 by American Society for Pharmacology and Experimental Therapeutics