Stable expression of human cytochrome P450IA2 cDNA in a human lymphoblastoid cell line: role of the enzyme in the metabolic activation of aflatoxin B1.
A human lymphoblastoid cell line stably expressing a human cytochrome P450IA2 cDNA was developed. This recombinant cell line displayed P450IA2 protein and estradiol 2-hydroxylase activity, neither of which was detected in the parental cell line. The recombinant cell line was also approximately 1000-fold more sensitive to the cytotoxicity and mutagenicity of the carcinogenic mycotoxin aflatoxin B1 than was the parent cell line. The increase in mutagenicity was supported by a corresponding increase in the level of aflatoxin B1 binding to DNA in cells expressing P450IA2 relative to control cells.
Crespi
C L
CL
Gentest Corporation, Woburn, Massachusetts 01801.
Steimel
D T
DT
Aoyama
T
T
Gelboin
H V
HV
Gonzalez
F J
FJ
D016604:Aflatoxin B1; D000348:Aflatoxins / Q000378:metabolism* / Q000633:toxicity; D001402:B-Lymphocytes; D001711:Biotransformation; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D009153:Mutagens; D013250:Steroid Hydroxylases / Q000378:metabolism; D014162:Transfection
D000348:Aflatoxins; D009153:Mutagens; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D016604:Aflatoxin B1; D013250:Steroid Hydroxylases; D019363:Cytochrome P-450 CYP1A1; C020120:estrogen 2-hydroxylase