Apiaceous vegetable intake modulates expression of DNA damage response genes and microRNA in the rat colon

Abstract

We examined chemo-preventive mechanisms of apiaceous vegetable intake against 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Rats fed either a purified diet, or purified diet supplemented with 21% apiaceous vegetables (API), were injected with PhIP after 6 d of feeding and colons harvested 24 h later. There was a trend for increased colonic mRNA expression of P-glycoprotein, a PhIP efflux transporter. No DNA damage response genes were up-regulated by API but 13 of these genes were down-regulated, compared to the positive control group, which may have been due to formation of fewer PhIP-DNA adducts. In colonic miRNA profiling, 11 out of 421 miRNAs were modulated in the API group, 3 of which target 19 mRNAs involved in cancer signaling pathways. API increased miR-19a, which targets Ccnd1, a potential oncogene responsible for G1-S cell cycle progression. In conclusion, apiaceous vegetable intake may be chemopreventive through modification of miRNA expression as well as P-glycoprotein expression in colon.