The action of a dietary retinoid on gene expression and cancer induction in electron-irradiated rat skin.
Current models of radiation carcinogenesis generally assume that the DNA is damaged in a variety of ways by the radiation and that subsequent cell divisions contribute to the conversion of the damage to heritable mutations. Cancer may seem complex and intractable, but its complexity provides multiple opportunities for preventive interventions. Mitotic inhibitors are among the strongest cancer preventive agents, not only slowing the growth rate of preneoplasias but also increasing the fidelity of DNA repair processes. Ionizing radiation, including electrons, is a strong inducer of cancer in rat skin, and dietary retinoids have shown potent cancer preventive activity in the same system. A non-toxic dietary dose of retinyl acetate altered gene expression levels 24 hours after electron irradiation of rat skin. Of the 8740 genes on an Affymetrix rat expression array, the radiation significantly (5 fold or higher) altered 188, while the retinoid altered 231, including 16 radiation-altered genes that were reversely altered. While radiation strongly affected the expression of stress response, immune/inflammation and nucleic acid metabolism genes, the retinoid most strongly affected proliferation-related genes, including some significant reversals, such as, keratin 14, retinol binding protein, and calcium binding proteins. These results point to reversal of proliferation-relevant genes as a likely basis for the anti-radiogenic effects of dietary retinyl acetate.
Burns
Fredric J
FJ
Department of Environmental Medicine, NYU School of Medicine, New York, NY 10016, USA. burns@env.med.nyu.edu
Chen
Shuaili
S
Xu
Guijuan
G
Wu
Feng
F
Tang
Moon-Shong
MS
D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage*; D002455:Cell Division / Q000187:drug effects; D004032:Diet; D004224:Diterpenes; D004583:Electrons; D015870:Gene Expression / Q000187:drug effects* / Q000528:radiation effects*; D009381:Neoplasms, Radiation-Induced / Q000473:pathology*; D051381:Rats; D000084562:Retinyl Esters; D012867:Skin / Q000187:drug effects* / Q000528:radiation effects*; D014801:Vitamin A / Q000008:administration & dosage* / Q000031:analogs & derivatives*
D016588:Anticarcinogenic Agents; D004224:Diterpenes; D000084562:Retinyl Esters; D014801:Vitamin A; C009166:retinol acetate