The effects of consumption of cooked/cured meat and green tea catechins on xenobiotic metabolism and longevity in F344 rats

This thesis presents an investigation of the effect of consumption of cooked/cured meat and green tea catechins on xenobiotic metabolism and chronic disease patterns in Fischer 344 rats. Consumption of cooked and cured meat has been associated with increased risk of gastrointestinal cancer. Consumption of green tea catechins has been associated with decreased risk for gastrointestinal cancers. Cooked/cured meat contains known secondary carcinogens, including heterocyclic amines (HCA), polycyclic aromatic hydrocarbons (PAH) and nitrosamines (NA). HCA, PAH and NA are bioactivated to carcinogens in the body by the cytochrome p450 isoforms CYP1A1/A2 and CYP2E1. Green tea catechins are thought to alter the expression and function of these p450 enzymes, as well as the protective conjugation enzymes, including glutathione S-transferases (GST) and UDP-glucuronyl transferases (UGT). To examine this we explored the effect of: (1) lifetime feeding of hot dog, and hot dog containing green tea on the morbidity and the incidence of gastrointestinal cancers in F344 rats (2) chronic consumption of hot dog or hot dog containing green tea catechins on CYP1A1/A2, CYP2E1 and AhR induction and (3) chronic consumption of green tea catechins or hot dog containing green tea on induction of GST and UGT. Rats fed hot dog and hot dog containing green tea diets had a lower incidence of large granular lymphocytic (LGL) leukemia than rats fed the control diet. In addition, rats fed hot dog and hot dog containing green tea diets did not develop gastrointestinal cancers. Consumption of hot dog resulted in upregulation CYP1A1/A2 and 2E1 in some gastrointestinal tissues and green tea catechins inhibited this upregulation in some tissues. Green tea catechins and hot dog consumption resulted in upregulation in UGT and GST in some gastrointestinal tissues. In conclusion, rats are resistant to intestinal carcinogenesis induced by consumption of cooked/cured meat, and this diet with supplemental catechins may protect against the development of LGL, which is a common cause of mortality in F344 rats.