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© 1989 Oxford University Press

research-article

Suppression of Humoral Immune Responses by Dialkylnitrosamines: Structure-Activity Relationships1

NORBERT E. KAMINSKI*, STEPHEN D. JORDAN*, DENNIS PAGE{dagger}, BYUNG SAM KIM{ddagger} and MICHAEL HOLSAPPLE*

*Department of Pharmacology and Toxicologyy. Medical College of Virginia/Virginia Commonwealth University Richmond, Virginia 23298 {dagger}Department of Oral Patho1og.v. Medical College of Virginia/Virginia Commonwealth University Richmond, Virginia 23298 {ddagger}Department of Biological Sciences and Engineering. Korea Advanced institute of Science and Technology Seoul. Korea

Received February 17, 1988; accepted July 18, 1988

Suppression of Humoral Immune Responses by Dialkylnitrosamines: Structure-Activity Relationships. KAMINSKI, N. E., JORDAN, S. D., PAGE, D., KIM, B. S., AND HOLSAPPLE, M. P. (1989). Fundam. Appl Toxicol 12,321-332. Comparisons between chemical structure of N, N-dialkylnitrosamine congeners and their ability to alter the Day 4 IgM antibody response to sRBC, body weights. and organ weights of female B6C3F1 mice were investigated. Short-chain nitrosamine congeners were selected for these studies on the basis of two criteria: (1) congeners wth symmetrical aliphatic chain length [N-nitrosodimethylamine (DMN), N-nitrosodiethylamine (DEN), N-nitrdipropylamine (DPN), N-nitrosodibutylamine (DBN)] and (2) congeners possessing an N-methyl group [N-nitrosomethylethylamine (MEN), N-nitrosomethylpropylamine (MPN), and N-nitrosomethylbutylamine (MBN)]. The immunotoxicity of each congener was evaluated based on the compound's ability to suppress the in vivo sRBC antibody response following 7 consecutive days of treatment. An ED50 dose was calculated, using a linear regression analysis, for each congener and represents the millimoles of congener per kilogram body weight required to cause a 50% suppression of the sRBC response. These studies demonstrated two general trends: (1) those dialkylnitrosamine congeners that possessed an N-methyl group were most immunotoxic and exhibited comparable ED50 concentrations (42-183 µmol/kg); and (2) dialkylnitrosamine congeners possessing symmetrical aliphatic chains demonstrated an inverse relationship between aliphatic chain length and immunotoxic potency—DMN (62 µmol/kg) > DEN (276 µmol/kg) > DPN (467 µmol/kg) > DMN (1557 µmol/kg). Comparisons were also made between the immunotoxic potency of various nitrosamine congeners in the whole animal and their potency in an in vitro hepatocyte-spleen cell coculture system.


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