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 sh own to exert anti-carcinogenic activity in several target organs. In this s tudy, we have investigated the effects of I3C on cigarette smoke-related li pophilic DNA adduct formation, potentially a key step in chemical carcinoge nesis. Female Sprague-Dawley rats were exposed to sidestream cigarette smok e in a whole-body exposure chamber for 6 h per day, 7 days a week for 4 wee ks. Control animals received only vehicle while the intervention groups rec eived I3C (1.36 or 3.40 mmol/kg, b.wt.) daily by gavage starting from 1 wee k prior to smoke initiation until the end of the experiment. Analysis of ti ssue DNA by nuclease Pi-mediated P-32-postlabeling showed one major and sev eral minor smoke-related adducts in lung, trachea, heart and bladder. The h igh dose of I3C significantly inhibited the major adducts in lung (#5) and trachea (#3) by 55% each; minor adducts were slightly inhibited (20-40%). T he 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 (> 6 5%) by high dose of I3C approaching adduct levels achieved in sham-exposed rats. A small but statistically significant decrease in the smoke-related D NA 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 signific ance remains unknown. These data show significant inhibition of cigarette s moke-related DNA adducts by I3C, particularly in the lung, trachea, and bla dder, (C) 2000 Published by Elsevier Science B.V.