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 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.

[1]  H. Bartsch,et al.  Induction of cytochrome P450 2A6 expression in humans by the carcinogenic parasite infection, opisthorchiasis viverrini. , 1996, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[2]  H. Esumi,et al.  Thiocyanate-independent nitrosation in humans with carcinogenic parasite infection. , 1996, Carcinogenesis.

[3]  N. Mabbott,et al.  Nitric oxide‐mediated suppression of T cell responses during Trypanosoma brucei infection: soluble trypanosome products and interferon‐γ are synergistic inducers of nitric oxide synthase , 1996, European journal of immunology.

[4]  I. Charles,et al.  Altered immune responses in mice lacking inducible nitric oxide synthase , 1995, Nature.

[5]  F. Liew,et al.  Regulation of lymphocyte functions by nitric oxide. , 1995, Current opinion in immunology.

[6]  M. Haswell-Elkins,et al.  Cross‐sectional study of Opisthorchis viverrini infection and cholangiocarcinoma in communities within a high‐risk area in northeast thailand , 1994, International journal of cancer.

[7]  C. Wild,et al.  Association of liver fluke (Opisthorchis viverrini) infestation with increased expression of cytochrome p450 and carcinogen metabolism in male hamster liver1,2 , 1994, Molecular carcinogenesis.

[8]  M. Haswell-Elkins,et al.  Parasite-associated morbidity: liver fluke infection and bile duct cancer in northeast Thailand. , 1994, International journal for parasitology.

[9]  K. Rockett,et al.  Possible role of nitric oxide in malarial immunosuppression , 1994, Parasite immunology.

[10]  A. Taylor-Robinson,et al.  Regulation of the immune response by nitric oxide differentially produced by T helper type 1 and T helper type 2 cells , 1994, European journal of immunology.

[11]  H. Esumi,et al.  Liver fluke infection and cholangiocarcinoma: model of endogenous nitric oxide and extragastric nitrosation in human carcinogenesis. , 1994, Mutation research.

[12]  H. Rim,et al.  Promoting role of Clonorchis sinensis infection on induction of cholangiocarcinoma during two-step carcinogenesis. , 1994, The Korean journal of parasitology.

[13]  H. Bartsch,et al.  Increased nitrosamine and nitrate biosynthesis mediated by nitric oxide synthase induced in hamsters infected with liver fluke (Opisthorchis viverrini). , 1994, Carcinogenesis.

[14]  S. Tannenbaum,et al.  DNA damage and mutation in human cells exposed to nitric oxide in vitro. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[15]  T. Cebula,et al.  DNA deaminating ability and genotoxicity of nitric oxide and its progenitors. , 1991, Science.

[16]  J. Convit,et al.  Differing lymphokine profiles of functional subsets of human CD4 and CD8 T cell clones. , 1991, Science.

[17]  S. Kaufmann,et al.  The role of T-cell subsets and cytokines in the regulation of infection. , 1991, Immunology today.

[18]  B. Tennant,et al.  Elevated formation of nitrate and N-nitrosodimethylamine in woodchucks (Marmota monax) associated with chronic woodchuck hepatitis virus infection. , 1991, Cancer research.

[19]  T. Sugimura,et al.  L-arginine-dependent formation of N-nitrosamines by the cytosol of macrophages activated with lipopolysaccharide and interferon-gamma. , 1991, Carcinogenesis.

[20]  M. Haswell-Elkins,et al.  Immune responsiveness and parasite‐specific antibody levels in human hepatobiliary disease associated with Opisthorchis viverrini infection , 1991, Clinical and experimental immunology.

[21]  J. Chawla,et al.  Increased urinary nitrosamine excretion in paraplegic patients. , 1991, Carcinogenesis.

[22]  S. Tannenbaum,et al.  Endogenous incorporation of nitric oxide from L-arginine into N-nitrosomorpholine stimulated by Escherichia coli lipopolysaccharide in the rat. , 1991, Carcinogenesis.

[23]  H. Bartsch,et al.  Endogenous nitrosamines and liver fluke as risk factors for cholangiocarcinoma in Thailand. , 1991, IARC scientific publications.

[24]  J. Hibbs,et al.  The role of nitrogen oxides as effector molecules of parasite killing. , 1990, Parasitology today.

[25]  S. Moncada,et al.  Macrophage killing of Leishmania parasite in vivo is mediated by nitric oxide from L-arginine. , 1990, Journal of immunology.

[26]  S. Dunn,et al.  N-nitrosodimethylamine blood levels in patients with chronic renal failure: modulation of levels by ethanol and ascorbic acid. , 1990, Journal of the National Cancer Institute.

[27]  H. Bartsch,et al.  Exposure of humans to endogenous N-nitroso compounds: implications in cancer etiology. , 1990, Mutation research.

[28]  S. Abramson,et al.  Regulation of immunoglobulin production in hyperimmunoglobulin E recurrent-infection syndrome by interferon gamma. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[29]  B. Spiegelhalder,et al.  Urinary excretion of nitrate, nitrite and N-nitroso compounds in Schistosomiasis and bilharzia bladder cancer patients. , 1989, Carcinogenesis.

[30]  S. Tannenbaum,et al.  Mechanisms of endogenous nitrosation. , 1989, Cancer surveys.

[31]  W. Deen,et al.  Theoretical model for predicting rates of nitrosamine and nitrosamide formation in the human stomach. , 1988, Carcinogenesis.

[32]  P. Magee,et al.  Pharmacokinetics of N-nitrosodimethylamine in swine. , 1988, Carcinogenesis.

[33]  J. Lamb,et al.  The use of nitrocellulose immunoblots for the analysis of antigen recognition by T lymphocytes. , 1988, Journal of immunological methods.

[34]  I. Clark.  Cell-mediated immunity in protection and pathology of malaria. , 1987, Parasitology today.

[35]  S. Tannenbaum,et al.  Nitrosation of amines by stimulated macrophages. , 1987, Carcinogenesis.

[36]  H. Pylypiw,et al.  Pharmacokinetics of N-nitrosodimethylamine in beagles. , 1987, Cancer research.

[37]  S. Srianujata,et al.  High urinary excretion of nitrate and N-nitrosoproline in opisthorchiasis subjects. , 1987, IARC scientific publications.

[38]  H. Bartsch,et al.  N-nitrosamine formation in urinary-tract infections. , 1987, IARC scientific publications.

[39]  D. Flavell,et al.  Opisthorchis viverrini: pathogenesis of infection in immunodeprived hamsters , 1986, Parasite immunology.

[40]  M. C. Archer,et al.  Alcohol consumption does not lead to urinary excretion of N-nitrosodimethylamine in the fasting human. , 1986, Carcinogenesis.

[41]  B. Spiegelhalder,et al.  In vivo nitrosation of amidopyrine in humans: use of 'ethanol effect' for biological monitoring of N-nitrosodimethylamine in urine. , 1985, Carcinogenesis.

[42]  S. Lucas,et al.  Promotion of N-nitrosodimethylamine-initiated bile duct carcinogenesis in the hamster by the human liver fluke, Opisthorchis viverrini. , 1983, Carcinogenesis.

[43]  H. Bartsch,et al.  Quantitative estimation of endogenous nitrosation in humans by monitoring N-nitrosoproline excreted in the urine. , 1981, Cancer research.

[44]  K. Warren,et al.  Factors that modify the cellular-immune response in patients infected by Schistosoma mansoni. , 1980, Journal of immunology.

[45]  N. Bhamarapravati,et al.  Effects of dimethylnitrosamine on induction of cholangiocarcinoma in Opisthorchis viverrini-infected Syrian golden hamsters. , 1978, Cancer research.

[46]  S. Kyrtopoulos,et al.  Rapid formation of carcinogenic N-nitrosamines in aqueous alkaline solutions. , 1977, British Journal of Cancer.

[47]  S. Mirvish.  Kinetics of dimethylamine nitrosation in relation to nitrosamine carcinogenesis. , 1970, Journal of the National Cancer Institute.