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Title: Cytochrome P-450 regulation in human tumour-derived cell lines
Author: Stanley, Lesley A.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1992
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Cytochrome P-450s (P-450s) comprise a polymorphic multigene family of haem-containing enzymes which are essential to the Phase I metabolism of xenobiotics. They take part in activation and detoxification of carcinogens and anticancer drugs; thus an understanding of these enzymes is essential to the prevention and treatment of cancer. Induction of P-450s by drugs and carcinogens has been extensively studied; endogenous regulation of P-450s also occurs during normal development and disease. The aim of this project was to develop an in vitro system in which to study P-450 induction and modulation during inflammation. P-450 regulation in five human tumour-derived cell lines, HepG2 (liver) NCI H322, NCI H358 (lung), HT29 and LS174T (colon) was examined. The liver cell line was chosen because of this organ's importance in xenobiotic metabolism and the known effects of inflammation on hepatic P-450 expression; the lung and colon lines were selected because these organs also express P-450s and are subject to inflammatory disorders which may be involved in tumorigenesis. The cell lines expressed variable levels of 7-ethoxyresorufin O-deethylase (EROD) which could be induced by benzanthracene (BA); after BA treatment isozyme MC1b could be detected by Western blot analysis. The lung cell line NCI H322 was selected for further study. Induction of isozyme MC1b in this cell line involved an increase in steady-state mRNA expression; further experiments established suitable conditions for induction (5μg/ml BA in RPMI medium containing 10% foetal calf serum). The MTT assay was used to estimate the toxicity of P-450 inducers towards HEPG2 and NCI H322 cells and to examine the effects of P-450 induction on the toxicity of benzo(a)pyrene (B(a)P) and cyclophosphamide.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available