RELATIONSHIPS BETWEEN THE SYNTHESIS OF N-NITROSODIMETHYLAMINE AND IMMUNE-RESPONSES TO CHRONIC INFECTION WITH THE CARCINOGENIC PARASITE, OPISTHORCHIS-VIVERRINI, IN MEN

This study investigated the relationship between immune responses to i nfection,vith the liver fluke, Opisthorchis viverrini, and the synthes is of the carcinogen, N-nitrosodimethylamine (NDMA) in humans. It also examined associations bet,veen synthesis of nitric oxide (NO) and nit rosation of amines, in vivo. Antibody and T cell responses to fluke an tigens and post-alcohol urinary NDMA excretion were assessed among thr ee groups of 40-50 men with no, moderate and heavy liver fluke infecti on. Markers of NO synthesis (nitrate, nitrite) and nitrosation (nitros amino acids) were also measured in biological fluids. Assessments were carried out under controlled conditions which minimised intake of exo genous nitrate and nitrite and were carried out at two time points, na mely before and 4 months after elimination of the infection with prazi quantel treatment. No statistically significant variation was observed in the amount of NDMA excreted between the 3 groups. However, during active infection, a strong negative association was observed between i n vitro lymphoproliferative responses to some liver fluke antigens and NDMA excretion. After treatment this association was reduced. Multiva riate statistical models revealed a highly significant relationship be tween NDMA levels and urinary nitrate, stimulation indices for two T c ell responses to two parasite antigens (MW 37 kDa and 110 kDa) and gal l bladder dimensions. NDMA levels after treatment were best described by the ratio between parasite-specific IgG2 and IgE, background levels of T cell proliferation, a urinary marker of nitrosation (N-nitrosoth ioproline) and usual level of alcohol consumption. These results sugge st that individual background immunologic activity, parasite-specific responses and/or parasite products and NO synthesis are important dete rminants of endogenous generation of nitrosamines in O. viverrini-infe cted humans.