Carcinogenesis, Vol 19, 485-491, Copyright © 1998 by Oxford University Press
S Satarug, MR Haswell-Elkins, P Sithithaworn, H Bartsch, H Ohshima, M Tsuda, P Mairiang, E Mairiang, P Yongvanit, H Esumi and DB Elkins
This study investigated the relationship between immune responses to
infection with the liver fluke, Opisthorchis viverrini, and the synthesis
of the carcinogen, N-nitrosodimethylamine (NDMA) in humans. It also
examined associations between synthesis of nitric oxide (NO) and
nitrosation of amines, in vivo. Antibody and T cell responses to fluke
antigens and post-alcohol urinary NDMA excretion were assessed among three
groups of 40-50 men with no, moderate and heavy liver fluke infection.
Markers of NO synthesis (nitrate, nitrite) and nitrosation (nitrosamino
acids) were also measured in biological fluids. Assessments were carried
out under controlled conditions which minimised intake of exogenous nitrate
and nitrite and were carried out at two time points, namely before and 4
months after elimination of the infection with praziquantel 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 in vitro lymphoproliferative
responses to some liver fluke antigens and NDMA excretion. After treatment
this association was reduced. Multivariate statistical models revealed a
highly significant relationship between NDMA levels and urinary nitrate,
stimulation indices for two T cell responses to two parasite antigens (MW
37 kDa and 110 kDa) and gall 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-nitrosothioproline) and usual level of alcohol consumption.
These results suggest that individual background immunologic activity,
parasite-specific responses and/or parasite products and NO synthesis are
important determinants of endogenous generation of nitrosamines in O.
viverrini-infected humans.
ARTICLES
Relationships between the synthesis of N-nitrosodimethylamine and immune responses to chronic infection with the carcinogenic parasite, Opisthorchis viverrini, in men
National Research Centre for Environmental Toxicology, Coopers Plains, Queensland, Australia. s.satarug@mailbox.ug.edu.au
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