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Title: Metabolism and cytotoxicity of aflatoxin B1 in rat liver cells
Author: Metcalfe, Sylvia A.
ISNI:       0000 0001 3395 6429
Awarding Body: University of Surrey
Current Institution: University of Surrey
Date of Award: 1980
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Freshly isolated rat hepatocytes were found to metabolise 14C-aflatoxin B1 (AFB1) to aflatoxins M1 (AFM1) and Q1(AFQ1), and to radiolabelled polar material, presumably conjugates, as analysed by high-performance liquid chromatography, thin-layer chromatography and radioactive counting. Feeding AFB1 to rats enhanced production of polar material only, whereas phenobarbitone and 3-methylcholanthrene (3-MC) pretreatments both enhanced the rate of AFB1 metabolism and the production of polar material, with increased AFQ1 and AFM1 respectively. Formation of AFQ1 appeared to be mediated via cytochrome P450-linked enzymes whereas cytochrome P448-linked enzymes appeared to be involved in AFM1 production. Hepatocytes cultured for 24 hr from control and pretreated rats also metabolised AFB1 but not as efficiently as the corresponding freshly isolated cells. Metabolism of AFB1 and cytochrome P450 contents were undetected in a liver-derived epithelial-like dividing cell line, BL8L. AFB1 caused marked and rapid (1 hr) inhibition of ribonucleic acid (RNA) synthesis and pronounced but less rapid inhibition of protein synthesis. In both freshly isolated and 24 hr cultured hepatocytes from control rats (AFB1 concentration, 0.01-0.5 μq ml-1). Pretreatments with phenobarbitone and 3-MC resulted in reduced AFB1 inhibition of RNA and protein syntheses at the lower concentrations of AFB1 only, whereas cells from AFB1 fed rats were much less susceptible to AFB1 inhibition of these processes at all concentrations. In BL8L cells, AFB1 caused considerable inhibition of deoxyribonucleic acid (DNA) synthesis following 24 hr incubation, but inhibition of RNA and protein syntheses was minimal. In cells from control rats, AFB1 addition resulted in pronounced cytotoxicity (as assessed by morphological criteria of viability and trypan blue exclusion) following 4 hr incubation. However, in cells from phenobarbitone and 3-MC pretreated rats, cytotoxicity was marked at high AFB1 concentrations, whereas AFB1 feeding caused resistance to the cytotoxic action of AFB1 at all concentrations. The BL8L cells were much less susceptible to AFB1 cytotoxicity than in the hepatocytes. It is concluded that cytotoxicity of AFB1 is increased as a result of metabolism and that AFB1 feeding, in particular, confers resistance against AFB1 cytotoxicity.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Toxicology & poisons