Comparison of DNA adduct levels associated with exogenous and endogenous exposures in human pancreas in relation to metabolic genotype

Haplotype ofN-Acetyltransferase 1 and 2 and Risk of Pancreatic Cancer

“…It has been proposed that tissuespecific NAT-catalyzed O-acetylation of the N-hydroxyaromatic amines is an important determinant of DNA adduct formation (34). Previous studies on NAT1 genotype and DNA adducts in the human pancreas have been limited (35,36). The regulatory mechanisms of NAT1 in the human pancreas deserve further investigation.…”

Role of inflammation in pancreatic carcinogenesis and the implications for future therapy

“…Oxidative DNA adducts and MDA have been found to be elevated in patients with chronic pancreatitis [32,33,171] and in normal pancreatic tissue [172] . Levels of the oxidative DNA adduct, 8-OH-dg, and malondialdehyde have been reported to be higher in human pancreatic tumour tissue [173,174] .…”

Gene-Environment Interactions in Pancreatic Cancer

“…Pancreas tissue can activate arylamines, which are potential pancreatic carcinogens [22,[25][26][27]. It has been proposed that this class of compounds could reach the liver, where they would be either deactivated by N-acetyltransferase 2 or activated by CYP1A2 through hydroxylation.…”

“…Although there is evidence for a role of steroid and digestive hormones [6,34], such as secretin and cholecystokinin, in the promotion of this neoplasm, these factors have not been considered in previous case-control studies. Similarly, the presence of endogenous DNA adducts associated with endogenous oxidative stress or lipid peroxidation has been detected in pancreatic tissue, while they have not been measured in epidemiological studies [26,35]. Third, the relationship between the endocrine and exocrine components of the pancreas could play a role in the pathogenesis of cancer.…”