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The effects of chronic ethanol administration on polyamine content during dimethylhydrazine-induced colorectal carcinogenesis in the rat
Authors:McGarrity  Thomas J; Peiffer  Laurie P; Colony  Pamela C; Pegg  Anthony E
Institution:Departments of Medicine, The Milton S. Hershey Medical Centre, The Pennsylvania State University Hershey, PA 17033, USA
1Anatomy, The Milton S. Hershey Medical Centre, The Pennsylvania State University Hershey, PA 17033, USA
2Physiology, The Milton S.Hershey Medical Center, The Pennsylvania State University Hershey, PA 17033, USA
Abstract:Chronic ethanol (EtOH) consumption has been implicated as aco-carcinogen, selectively promoting rectal tumor formation.We studied the effects of EtOH consumption on tumor formationand polyamine content (putrescine, spermidine and spermine)in proximal and distal colon and rectum of Sprague-Dawley ratstreated with the procarcinogen 1,2-dimethylhydrazine (DMH).Sixty-four adult male rats were pair fed nutritionally completeliquid diets with 36% of calories supplied as EtOH or isocaloriccarbohydrates. Both groups received 4 weeks of the liquid dietfollowed by 4 weeks of standard laboratory chow during which50% of the rats in each group received DMH (30 mg/kg) or vehicles.c. weekly. This cycle was repeated four times (32 weeks).Animals were sacrificed at the end of each 8 week cycle andnormal appearing and available tumor bearing tissue from proximaland distal colon and rectum was obtained for polyamine contentand histology. Five animals, unexposed to DMH or EtOH servedas baseline controls. There were no consistent regional differencesin putrescine, spermidine or spermine of baseline controls.A progressive decrease in tissue putrescine was seen in allthree regions of the control group and was significant at 24and 32 weeks versus baseline controls. In all three regions,chronic EtOH consumption prevented the decrease in tissue putrescine.Spermidine content was also significantly increased in the distalcolon of EtOH-treated animals compared to baseline values. Consistentchanges in spermine content were seen in any treatment groupor region. A significant increase in putrescine content of normalappearing and tumor-bearing tissue of DMH treated animals at32 weeks was noted. Chronic EtOH administration did not augmentrectal or colonic polyamine content in DMH-treated animals.Likewise, chronic EtOH consumption did not alter the number,size or distribution of large bowel tumors of DMH treated animals.
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