Inhibition of cigarette smoke-related DNA adducts in rat tissues by indole-3-carbinol

被引:20
作者
Arif, JM
Gairola, CG
Kelloff, GJ
Lubet, RA
Gupta, RC
机构
[1] Univ Kentucky, Dept Prevent Med & Environm Hlth, Lexington, KY 40536 USA
[2] Univ Kentucky, Tobacco & Hlth Res Inst, Lexington, KY 40536 USA
[3] NCI, Dept Chemoprevent, Invest Branch, Bethesda, MD 20892 USA
关键词
indole-3-carbinol; cigarette smoke; DNA adducts; P-32-postlabeling; rat lung;
D O I
10.1016/S0027-5107(00)00010-5
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Indole-3-carbinol (I3C) found in various cruciferous vegetables has been shown to exert anti-carcinogenic activity in several target organs. In this study, we have investigated the effects of I3C on cigarette smoke-related lipophilic DNA adduct formation, potentially a key step in chemical carcinogenesis. Female Sprague-Dawley rats were exposed to sidestream cigarette smoke in a whole-body exposure chamber for 6 h per day, 7 days a week for 4 weeks. Control animals received only vehicle while the intervention groups received I3C (1.36 or 3.40 mmol/kg, b.wt.) daily by gavage starting from 1 week prior to smoke initiation until the end of the experiment. Analysis of tissue DNA by nuclease Pi-mediated P-32-postlabeling showed one major and several minor smoke-related adducts in lung, trachea, heart and bladder. The high dose of I3C significantly inhibited the major adducts in lung (#5) and trachea (#3) by 55% each; minor adducts were slightly inhibited (20-40%). The low dose of I3C showed lesser degree of inhibition (30-40%) in both lung and trachea; however, it was found statistically significant in lung only. The major smoke-related adduct in bladder (#2) was strongly inhibited (> 65%) by high dose of I3C approaching adduct levels achieved in sham-exposed rats. A small but statistically significant decrease in the smoke-related DNA adduct (#5) in heart tissue was also observed by intervention with high dose I3C. Low levels (30-50 adducts/10(10) nucleotides) of I3C-derived DNA adducts were also found in all the tissues examined although their significance remains unknown. These data show significant inhibition of cigarette smoke-related DNA adducts by I3C, particularly in the lung, trachea, and bladder, (C) 2000 Published by Elsevier Science B.V.
引用
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页码:11 / 18
页数:8
相关论文
共 47 条
[2]  
[Anonymous], 1992, EPA600690006F OFF HL
[3]   Inhibition of cigarette smoke-related lipophilic DNA adducts in rat tissues by dietary oltipraz [J].
Arif, JM ;
Gairola, CG ;
Glauert, HP ;
Kelloff, GJ ;
Lubet, RA ;
Gupta, RC .
CARCINOGENESIS, 1998, 19 (08) :1515-1517
[4]  
Arif JM, 1997, INT J ONCOL, V11, P1227
[5]  
Arnao MB, 1996, BIOCHEM MOL BIOL INT, V39, P1125
[6]  
BAILEY GS, 1987, JNCI-J NATL CANCER I, V78, P931
[7]   Cytochrome P450: Structure, function, and generation of reactive oxygen species [J].
Bernhardt, R .
REVIEWS OF PHYSIOLOGY BIOCHEMISTRY AND PHARMACOLOGY, VOL 127, 1996, 127 :137-221
[8]   INHALED CIGARETTE-SMOKE INDUCES THE FORMATION OF DNA ADDUCTS IN LUNGS OF RATS [J].
BOND, JA ;
CHEN, BT ;
GRIFFITH, WC ;
MAUDERLY, JL .
TOXICOLOGY AND APPLIED PHARMACOLOGY, 1989, 99 (01) :161-172
[9]   Indole-3-carbinol - A novel approach to breast cancer prevention [J].
Bradlow, HL ;
Sepkovic, DW ;
Telang, NT ;
Osborne, MP .
CANCER PREVENTION: FROM THE LABORATORY TO THE CLINIC: IMPLICATIONS OF GENETIC, MOLECULAR, AND PREVENTIVE RESEARCH, 1995, 768 :180-200
[10]  
BRADLOW HL, 1994, CANCER EPIDEM BIOMAR, V3, P591