Comparison of CYP1A1 induction and genotoxicity in vitro as indicators of potentially harmful effects of environmental samples.
Cytochrome P450IA1 (CYP1A1) induction of Hepa-1 mouse and H4IIE rat hepatoma cell lines was compared using selected environmental samples. The results were in agreement for both cell lines: no induction was observed for the fly ash extract from peat combustion, an intermediate induction was found for the fly ash extract from biosludge combustion, and a strong induction was detected for natural peat extract. However, Hepa-1 responded to the samples more sensitively than did H4IIE: the half maximal induction (ED50) values for Hepa-1 were smaller than those for H4IIE. In a bacterial DNA repair assay without metabolic activation and in a mammalian sister chromatid exchange test in the presence of metabolic activation the samples were virtually non-genotoxic. Thus the CYP1A1-inducing potency and genotoxicity of the samples were not correlated. In light of these results, the CYP1A1 induction test might be a useful addition to conventional genotoxicity tests, which may fail to detect potentially harmful compounds/mixtures.
Department of Physiology, University of Kuopio, Finland.
P
P
Kopponen
R
R
Törrönen
J
J
Mäki-Paakkanen
A
A
von Wright
S
S
Kärenlampi
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis; D016466:CHO Cells; D002244:Carbon / Q000633:toxicity; D002460:Cell Line; D002478:Cells, Cultured; D060729:Coal Ash; D006224:Cricetinae; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004260:DNA Repair / Q000187:drug effects; D004269:DNA, Bacterial / Q000235:genetics; D004785:Environmental Pollutants / Q000633:toxicity*; D004790:Enzyme Induction / Q000187:drug effects; D004926:Escherichia coli / Q000235:genetics; D051379:Mice; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D010088:Oxidoreductases / Q000096:biosynthesis; D052638:Particulate Matter; D051381:Rats; D012854:Sister Chromatid Exchange / Q000187:drug effects; D012987:Soil; D014407:Tumor Cells, Cultured
D060729:Coal Ash; D004269:DNA, Bacterial; D004785:Environmental Pollutants; D009153:Mutagens; D052638:Particulate Matter; D012987:Soil; D002244:Carbon; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1