Inhibition of transformation in cultured rat tracheal epithelial cells by potential chemopreventive agents.
Twenty-eight compounds were screened for chemopreventive activity by using a rat tracheal epithelial cell transformation inhibition assay. In this new assay, chemicals were tested for their ability to inhibit the formation of transformed rat tracheal epithelial cell colonies which arise following exposure to the carcinogen benzo(a)pyrene. The 15 positive compounds were N-acetylcysteine, bismuththiol, calcium glucarate, (+/-) catechin, diallyl disulfide, glycaric acid, D-glucaro-1,4-lactone, N-(4-hydroxyphenyl)retinamide, D-limonene, mesna, retinoic acid, rutin, quercetin, silymarin, and taurine. In examining the nature of compounds that inhibited rat tracheal epithelial cell transformation, several possible chemopreventive mechanisms appeared to be predominant: compounds that were positive (a) increased glutathione levels or enhanced conjugation; (b) increased cytochrome P-450 activity; (c) displayed nucleophilic activity; or (d) induced differentiation. Thirteen compounds were negative in the rat tracheal epithelial transformation inhibition assay: crocetin, difluoromethylornithine, ellagic acid, esculetin, enoxalone, ibuprofen, levamisole, nordihydroguaiaretic acid, L-2-oxothiazolidine-4-carboxylate, piroxicam, sodium butyrate, D-alpha-tocopherol acetate, and polyethylene glycol 400. It was evident from these results that this assay would not detect compounds that were (a) anti-promoting in nature; (b) glutathione inhibitors; (c) differentiation inhibitors; (d) O6-methylguanine inhibitors; (e) organ specific; or (f) inactive. The rat tracheal epithelial cell transformation inhibition assay appeared to identify chemopreventive compounds that act at early stages of the carcinogenic process.
Steele
V E
VE
Environmental Sciences Division, NSI Technology Services Corporation, Research Triangle Park, North Carolina 27709.
Kelloff
G J
GJ
Wilkinson
B P
BP
Arnold
J T
JT
D000818:Animals; D000970:Antineoplastic Agents; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D004249:DNA Damage; D004848:Epithelium / Q000473:pathology; D017313:Fenretinide; D005937:Glucaric Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D011794:Quercetin / Q000494:pharmacology; D051381:Rats; D014132:Trachea / Q000473:pathology; D014212:Tretinoin / Q000031:analogs & derivatives / Q000494:pharmacology; D014810:Vitamin E / Q000494:pharmacology
D000970:Antineoplastic Agents; D014810:Vitamin E; D017313:Fenretinide; D014212:Tretinoin; D011794:Quercetin; D005937:Glucaric Acid