Inhibition of cigarette smoke-related DNA adducts in rat tissues by indole-3-carbinol.
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 P1-mediated 32P-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.
Arif
J M
JM
Department of Preventive Medicine and Environmental Health, Lexington, KY 40536-0305, USA.
Gairola
C G
CG
Kelloff
G J
GJ
Lubet
R A
RA
Gupta
R C
RC
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D004247:DNA / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D018736:DNA Adducts / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006321:Heart / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D010947:Plants, Toxic; D051381:Rats; D017207:Rats, Sprague-Dawley; D012906:Smoke / Q000009:adverse effects*; D014026:Nicotiana; D014132:Trachea / Q000187:drug effects / Q000378:metabolism; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism
D016588:Anticarcinogenic Agents; D018736:DNA Adducts; D007211:Indoles; D012906:Smoke; D004247:DNA; C016517:indole-3-carbinol