One of the mutagenic and carcinogenic heterocyclic amines (HCAs), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), is present in cooked foods and we are chronically exposed to this compound in our daily life. To study the role of HCAs in human carcinogenesis, we analyzed MeIQx-DNA adducts in 38 DNA samples obtained from surgical and autopsy specimens by the 32P-postlabeling method under adduct-intensification conditions with the modification of additional digestion with nuclease P1 and phosphodiesterase I after 32P-labeling at 5'-hydroxyl termini. This modified 32P-postlabeling method can detect N2-(deoxyguanosin-8-yl)-2-amino-3,8-dimethylimidazo- [4,5-f]quinoxaline 5'-monophosphate (5'-pdG-C8-MeIQx) at levels down to 1/10(10) nucleotides. The DNA samples from colon and rectum surgical specimens and a kidney taken at autopsy were found to contain an adduct spot corresponding to that of standard 5'-pdG-C8-MeIQx on TLC at levels of 14,18 and 1.8 per 10(10) nucleotides, respectively. Each adduct spot was extracted from TLC and identified to be 5'-pdG-C8-MeIQx by HPLC. Thus, MeIQx-DNA adducts actually exist in human tissues and this adduct formation may be involved in human cancer development.

No abstract

These results suggest that CYP1A1 and GSTM1 polymorphisms are linked to a propensity for PCa development.

Previous clinical study has demonstrated that 30-40% of patients undergoing pancreaticoduodenectomy (PD) developed hepatic steatosis. However, nonalcoholic steatohepatitis (NASH) is a little-known complication after PD. Recently we encountered two patients with PD who later developed NASH diagnosed by liver biopsy. Case 1 was a 79-year-old woman who underwent PD for intraductal papillary mucinous neoplasm (IPMN). She had postoperative severe diarrhea due to pseudomembranous enterocolitis. Severe liver dysfunction was observed on the 31st postoperative day. Abdominal computed tomography (CT) on the 32nd day showed remarkably decreased hepatic CT value of 6 HU. Immediate liver biopsy revealed NASH (Brunt criteria: grade 2, stage 2). Case 2 was a 71-year-old woman who underwent PD for IPMN. Liver biopsy on 70th postoperative day, which was performed for assessment of moderate liver dysfunction and decreased hepatic CT value of 44 HU, demonstrated simple steatosis. In the 21st postoperative month, she developed severe urinary tract infection together with marked liver dysfunction. Immediate liver biopsy revealed NASH (Brunt criteria: grade 1, stage 1). For each patient, treatment of infection and high-dose pancreatic enzyme supplements improved liver dysfunction and liver steatosis. Clinical features of our cases seem to support the current leading hypothesis of the pathogenesis of NASH, i.e., the two-hit theory.

No abstract