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Chemopreventive effect of perillyl alcohol on 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone induced tumorigenesis in (C3H/HeJ X A/J)F 1 mouse lung
Author(s) -
Lantry Laura E.,
Zhang Zhongqiu,
Gao Feng,
Crist Keith A.,
Wang Yian,
Kelloff Gary J.,
Lubet Ronald A.,
You Ming
Publication year - 1997
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/(sici)1097-4644(1997)27+<20::aid-jcb6>3.0.co;2-3
Subject(s) - bioassay , carcinogenesis , pharmacology , chemistry , disulfiram , alcohol , cancer research , biochemistry , biology , gene , genetics
This study was designed to test the chemopreventive potential of perillyl alcohol, an inhibitor of farnesyltransferase, in a mouse lung tumor bioassay. Perillyl alcohol is a naturally occurring monoterpene found in lavender, cherries, and mint. We have shown previously that the majority of lung tumors in this bioassay have an activating mutation in the K‐ ras gene, which occurs early in the development of mouse lung carcinogenesis. The Ras protein undergoes a series of post‐translational modifications, the first of which is farnesylation at the cysteine of the C‐terminal CAAX motif. These modifications lead to the anchoring of Ras p21 to the plasma membrane in its biologically active state. Activated Ras p21 couples growth regulatory signals from receptor tyrosine kinases to cytoplasmic second messengers. In a preliminary study, we determined the maximum tolerated dose of perillyl alcohol to be 75 mg/kg body weight. For the bioassay, 5‐week‐old male (C3H/HeJ X A/J) F1 hybrid mice were randomized into trial groups, and treated with perillyl alcohol three times per week i.p., starting 1 week prior to initiation with the carcinogen NNK, and continuing for 22 weeks after initiation. Our results show a 22% reduction in tumor incidence, and a 58% reduction in tumor multiplicity. Our study demonstrates that perillyl alcohol is an effective chemopreventive compound in the mouse lung tumor bioassay. J. Cell. Biochem. Suppl. 27:20–25. © 1998 Wiley‐Liss, Inc.