Journal Article

Grapefruit juice intake does not enhance but rather protects against aflatoxin B<sub>1</sub>-induced liver DNA damage through a reduction in hepatic CYP3A activity

Masaaki Miyata, Hiroki Takano, Lian Q. Guo, Kiyoshi Nagata and Yasushi Yamazoe

in Carcinogenesis

Volume 25, issue 2, pages 203-209
Published in print February 2004 | ISSN: 0143-3334
Published online February 2004 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgg194
Grapefruit juice intake does not enhance but rather protects against aflatoxin B1-induced liver DNA damage through a reduction in hepatic CYP3A activity

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Influence of grapefruit juice intake on aflatoxin B1 (AFB1)-induced liver DNA damage was examined using a Comet assay in F344 rats given 5 mg/kg AFB1 by gavage. Rats allowed free access to grapefruit juice for 5 days prior to AFB1 administration resulted in clearly reduced DNA damage in liver, to 65% of the level in rats that did not receive grapefruit juice. Furthermore, rats treated with grapefruit juice extract (100 mg/kg per os) for 5 days prior to AFB1 treatment also reduced the DNA damage to 74% of the level in rats that did not receive grapefruit juice. No significant differences in the portal blood and liver concentrations of AFB1 were observed between grapefruit juice intake rats and the controls. In an Ames assay with AFB1 using Salmonella typhimurium TA98, lower numbers of revertant colonies were detected with hepatic microsomes prepared from rats administered grapefruit juice, compared with those from control rats. Microsomal testosterone 6β-hydroxylation was also lower with rats given grapefruit juice than with control rats. Immunoblot analyses showed a significant decrease in hepatic CYP3A content, but not CYP1A and CYP2C content, in microsomes of grapefruit juice-treated rats than in non-treated rats. No significant difference in hepatic glutathione S-transferase (GST) activity and glutathione content was observed in the two groups. GSTA5 protein was not detected in hepatic cytosol of the two groups. In microsomal systems, grapefruit juice extract inhibited AFB1-induced mutagenesis in the presence of a microsomal activation system from livers of humans as well as rats. These results suggest that grapefruit juice intake suppresses AFB1-induced liver DNA damage through inactivation of the metabolic activation potency for AFB1 in rat liver.

Keywords: AFB1, aflatoxin B1; AFBO, aflatoxin B1 8,9-epoxide; CDNB, 1-chloro-2,4-dinitrobenzene; CYP, cytochrome P450; DCNB, 1,2-dichloro-4-nitrobenzene; GSH, reduced glutathione; GST, glutathione S-transferase; mEH, microsomal epoxide hydrolase; PhIP, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine

Journal Article.  5306 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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