The induction of benzo[a]pyrene-3-mono-oxygenase by singlet oxygen in liver cell culture is mediated by oxidation products of histidine.
The photochemical generation of excited states of oxygen by the mild illumination of culture medium containing 15 microM riboflavin results in a typical induction of benzo[a]pyrene-3-mono-oxygenase in cell lines derived from liver. However, the induction of the mono-oxygenase is not due to an excited state of oxygen directly activating the inducing mechanism inside the cell but is due to the oxidation of a component of the culture medium forming a stable inducer. The present work unequivocably shows that the component oxidised is histidine. The mild illumination of culture medium containing riboflavin therefore converts a physiological component of the medium which is not normally an inducer of the mono-oxygenase into a compound which is as effective an inducer as the classical inducer. The finding that singlet oxygen will oxidise a cell constituent into a powerful inducer is compatible with the hypothesis that excited states of oxygen and their oxidation products may play a central role in the induction of cytochrome P-450 and associated enzyme activities by many chemically unrelated inducers.
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis*; D001579:Benzopyrene Hydroxylase / Q000096:biosynthesis*; D002478:Cells, Cultured; D004790:Enzyme Induction; D006639:Histidine / Q000378:metabolism*; D008027:Light; D008099:Liver / Q000201:enzymology*; D010100:Oxygen; D010777:Photochemistry; D051381:Rats; D012256:Riboflavin
D000596:Amino Acids; D006639:Histidine; D001579:Benzopyrene Hydroxylase; D001189:Aryl Hydrocarbon Hydroxylases; D010100:Oxygen; D012256:Riboflavin