Preventive effects of quercetin against benzo[a]pyrene-induced DNA damages and pulmonary precancerous pathologic changes in mice.
The aim of this study was to investigate the preventive effects of quercetin against benzo[a]pyrene-induced blood lymphocyte DNA damages and pulmonary precancerous pathologic changes in mice, and to reveal the potential mechanism behind these effects. In this study, mice in quercetin-treated groups were given quercetin for 90 days. After one week of treatment, mice in the quercetin-treated groups and the positive control group received a single intraperitoneal dose of benzo[a]pyrene (100 mg/kg body weight). The results of single cell gel electrophoresis assay showed that the average lengths of the comet cell tail and DNA damage in the peripheral blood lymphocytes of mice induced by benzo[a]pyrene decreased significantly as a result of quercetin treatment dose-dependently. Light microscopic examination showed that the degrees of pulmonary precancerous pathologic changes in the quercetin-treated groups decreased significantly compared with those in the positive control group. Meanwhile, the cytochrome P4501A1-linked 7-ethoxyresorufin O-dealkylase activities in lung microsomes of mice decreased as the dose of quercetin increased. The results of this in vivo study revealed that quercetin had a significant preventive effect on benzo[a]pyrene-induced DNA damage, and had a potential chemopreventive effect on the carcinogenesis of lung cancer induced by benzo[a]pyrene. The mechanism of these effects of quercetin could be related to the inhibition of cytochrome P4501A1 activity.
Jin
Nian-zu
NZ
Institute of Toxicology, Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029, China. jinnianzu2004@yahoo.com
Zhu
Yan-ping
YP
Zhou
Jian-wei
JW
Mao
Li
L
Zhao
Ren-cheng
RC
Fang
Tai-hui
TH
Wang
Xin-ru
XR
D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity*; D020552:Comet Assay; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects*; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000473:pathology*; D008214:Lymphocytes / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D008861:Microsomes / Q000201:enzymology; D011230:Precancerous Conditions / Q000473:pathology* / Q000517:prevention & control*; D011794:Quercetin / Q000494:pharmacology*
D001564:Benzo(a)pyrene; D011794:Quercetin; D019363:Cytochrome P-450 CYP1A1