| ABSTRACT: |
|
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. |