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Year : 2018  |  Volume : 14  |  Issue : 58  |  Page : 548-553

Hepatic immune response to environmental carcinogens

1 Department of Medical Science, Respiratory Medicine and Allergology, Clinical Chemistry and Asthma Research Centre, Uppsala University and University Hospital, Uppsala, Sweden; Department of Microbiology/Immunology, College of Medicine, University of Sulaimani, Sulaimani, Iraq
2 Department of Medicine, College of Medicine, University of Sulaimani, Sulaimani, Iraq
3 Ministry of Higher Education and Scientific Research, Erbil, Iraq
4 College of Veterinary Medicine, University of Sulaimani, Sulaimani, Iraq
5 Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and London, Queen Mary, University of London, Charterhouse Square, London EC1M 6BQ, UK

Correspondence Address:
Kawa Amin
Department of Microbiology/Immunology, College of Medicine, University of Sulaimani, Sulaimani

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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/pm.pm_242_18

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Aim: Environmental carcinogenic substances contribute to increasing incidence of hepatocellular carcinoma (HCC). We employed a sensitive method for the detection of DNA damage combined with analysis of the immune response to gain better knowledge how environmental carcinogens mediate pathology. Materials and Methods: Rat hepatocytes were isolated and stimulated with carcinogenic substances for the assessment of DNA damage. The mycotoxin aflatoxin B1(AFB1), two heterocyclic amines from the cooking of meat amino-3-methylimidazo[4,5-f] quinoline (IQ) and 3-amino-1-methyl-5H-pyrido-(4,3-b)-indole (TRP-P-2), and protein extract from the fungus Lactarius necator were assayed. Unscheduled DNA synthesis in hepatocytes was measured by the incorporation of radioactive thymidine during DNA repair. Stimulation of hepatocyte/immune cell preparation with the substances and measurement of IFNγ release at different time points determined their ability to induce an inflammatory response. Results: DNA repair in the hepatocytes was induced in response to 10−7 M AFB1 and 10−9 M IQ. TRP-P-2 did not induce DNA repair; however, at 10−4 M, the fungus extract did this. Furthermore, liver-resident immune cells responded with differential production of IFNγ over time in response to stimulation by all the carcinogens, with AFB1 being the most potent. TRP-P-2 showed the most significant reduction in IFNγ response over time. Conclusion: DNA damage in hepatocytes induced by environmental substances was detected at low molecular concentrations. The system did provide novel evidence for hepatic carcinogenicity by the fungus L. necator. Analysis of the response by liver-resident immune cells to the substances suggested that highly mutagenic substances induce prolonged inflammatory response. Abbreviations used: HCC: Hepatocellular carcinoma, AFB1: Aflatoxin B1, IQ: Amino-3-methylimidazo[4,5-f] quinoline, TRP-P-2: 3-amino-1-methyl-5H-pyrido-(4,3-b)-indole, UDS: Unscheduled DNA synthesis, EGTA: Ethylene glycol-bis-(2-aminoethyl ether) N-N-N'-N'-tetraacetic acid, WME: Williams' medium E, 2-AAF: 2-Acetylaminofluorene, HBSS: Hanks' balanced salt solution, CYPs: Cytochrome p450 enzymes.

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