Cytochrome P3-450 cDNA encodes aflatoxin B1-4-hydroxylase
- PMID: 3137222
Cytochrome P3-450 cDNA encodes aflatoxin B1-4-hydroxylase
Abstract
Aflatoxin B1 (AFB1), a potent hepatocarcinogen and ubiquitous dietary contaminant in some countries, is detoxified to aflatoxin M1 (AFM1) via cytochrome P-450-mediated AFB1-4-hydroxylase. Genetic studies in mice have demonstrated that the expression of AFB1-4-hydroxylase is regulated by the aryl hydrocarbon locus and suggested that different cytochrome P-450 isozymes catalyze AFB1-4-hydroxylase and aryl hydrocarbon hydroxylase activities. We have now examined lysates from mammalian cells infected with recombinant vaccinia viruses containing expressible cytochrome P1-450 or P3-450 cDNAs for their ability to metabolize AFB1 to AFM1. Our results show that cytochrome P3-450 cDNA specifies AFB1-4-hydroxylase. This is the first direct assignment of a specific cytochrome P-450 to an AFB1 detoxification pathway. This finding may have relevance to the dietary modulation of AFB1 hepatocarcinogenesis.
Similar articles
-
The genetics of aflatoxin B1 metabolism. Association of the induction of aflatoxin B1-4-hydroxylase with the transcriptional activation of cytochrome P3-450 gene.J Biol Chem. 1988 Sep 5;263(25):12584-95. J Biol Chem. 1988. PMID: 3137229
-
Modulation of aflatoxin B1 biotransformation in rabbit pulmonary and hepatic microsomes.Toxicology. 1992 Aug;74(1):19-32. doi: 10.1016/0300-483x(92)90040-l. Toxicology. 1992. PMID: 1514185
-
Genetic expression of aflatoxin metabolism. Effects of 3-methylcholanthrene and beta-naphthoflavone on hepatic microsomal metabolism and mutagenic activation of aflatoxins.Biochem Pharmacol. 1983 Dec 15;32(24):3755-63. doi: 10.1016/0006-2952(83)90146-6. Biochem Pharmacol. 1983. PMID: 6318770
-
Cellular interactions and metabolism of aflatoxin: an update.Pharmacol Ther. 1995 Feb;65(2):163-92. doi: 10.1016/0163-7258(94)00054-7. Pharmacol Ther. 1995. PMID: 7540767 Review.
-
Aflatoxin B1 and M1: Biological Properties and Their Involvement in Cancer Development.Toxins (Basel). 2018 May 24;10(6):214. doi: 10.3390/toxins10060214. Toxins (Basel). 2018. PMID: 29794965 Free PMC article. Review.
Cited by
-
Human exposure to mycotoxins in Egypt.Mycotoxin Res. 2002 Mar;18(1):23-30. doi: 10.1007/BF02946136. Mycotoxin Res. 2002. PMID: 23605947
-
Genetic analysis of aflatoxin B1 activation in rat hepatoma cells.Mol Gen Genet. 1990 Jul;222(2-3):291-6. doi: 10.1007/BF00633831. Mol Gen Genet. 1990. PMID: 2125692
-
Microbial contamination of seven major weaning foods in Nigeria.J Health Popul Nutr. 2011 Aug;29(4):415-9. doi: 10.3329/jhpn.v29i4.8459. J Health Popul Nutr. 2011. PMID: 21957681 Free PMC article.
-
Involvement of cytochrome P450, glutathione S-transferase, and epoxide hydrolase in the metabolism of aflatoxin B1 and relevance to risk of human liver cancer.Environ Health Perspect. 1996 May;104 Suppl 3(Suppl 3):557-62. doi: 10.1289/ehp.96104s3557. Environ Health Perspect. 1996. PMID: 8781383 Free PMC article.
-
Distribution and induction of aflatoxin B1-9a-hydroxylase activity in rat liver parenchymal and non-parenchymal cells.Arch Toxicol. 1996;70(9):553-8. doi: 10.1007/s002040050312. Arch Toxicol. 1996. PMID: 8831905
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources