Effects of 2-amino-1-methyl-6-phenylimidazo [4, 5-b] pyridine (PhIP) on histopathology, oxidative stress, and expression of c-fos, c-jun and p16 in rat stomachs

Abstract: 2-Amino-1-methyl-6-phenylimidazo [4, 5-b] pyridine (PhIP) is one of the most abundant heterocyclic amines (HCAs) generated from overcooking meat at high temperatures. To understand the possible mechanism of PhIP-associated stomach cancer, the effects of PhIP on morphology, oxidative stress, gene expression of c-fos, c-jun and p16 in rat stomachs were investigated. The results showed that (1) 15mg/kg body weight PhIP induced obvious histopathological changes in gastric mucosa; (2) PhIP (10 and/or 15mg/kg) significantly decreased superoxide dismutase (SOD) and glutathioneperoxidase (GPx) activities, while increased catalase (CAT) activity compared with the control. With the elevated doses of PhIP, malondialdehyde (MDA) contents, protein carbonyl (PCO) contents and DNA–protein crosslinks (DPC) coefficients were significantly raised in a dose-dependent manner; (3) PhIP at the doses of 10mg/kg and/or 15mg/kg significantly inhibited p16 mRNA and protein expression, whereas enhanced c-fos and c-jun expression relative to control. The data indicated that PhIP could cause stomach injury, oxidative stress in rat stomachs as well as the activation of c-fos and c-jun and inactivation of p16, which may play a role in the pathogenesis of PhIP-associated stomach cancer. [Copyright &y& Elsevier]