The effects of chronic ethanol administration on polyamine content during dimethylhydrazine-induced colorectal carcinogenesis in the rat.
Chronic ethanol (EtOH) consumption has been implicated as a co-carcinogen, selectively promoting rectal tumor formation. We studied the effects of EtOH consumption on tumor formation and polyamine content (putrescine, spermidine and spermine) in proximal and distal colon and rectum of Sprague-Dawley rats treated with the procarcinogen 1,2-dimethylhydrazine (DMH). Sixty-four adult male rats were pair fed nutritionally complete liquid diets with 36% of calories supplied as EtOH or isocaloric carbohydrates. Both groups received 4 weeks of the liquid diet followed by 4 weeks of standard laboratory chow during which 50% of the rats in each group received DMH (30 mg/kg) or vehicle s.c. weekly. This cycle was repeated four times (32 weeks). Animals were sacrificed at the end of each 8 week cycle and normal appearing and available tumor bearing tissue from proximal and distal colon and rectum was obtained for polyamine content and histology. Five animals, unexposed to DMH or EtOH served as baseline controls. There were no consistent regional differences in putrescine, spermidine or spermine of baseline controls. A progressive decrease in tissue putrescine was seen in all three regions of the control group and was significant at 24 and 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 distal colon of EtOH-treated animals compared to baseline values. Consistent changes in spermine content were seen in any treatment group or region. A significant increase in putrescine content of normal appearing and tumor-bearing tissue of DMH treated animals at 32 weeks was noted. Chronic EtOH administration did not augment rectal 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.
McGarrity
T J
TJ
Department of Medicine, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.
Peiffer
L P
LP
Colony
P C
PC
Pegg
A E
AE
D000818:Animals; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D004127:Dimethylhydrazines; D000431:Ethanol / Q000008:administration & dosage*; D011073:Polyamines / Q000378:metabolism*; D011700:Putrescine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012007:Rectum / Q000187:drug effects / Q000378:metabolism*; D013095:Spermidine / Q000378:metabolism; D013096:Spermine / Q000378:metabolism
D004127:Dimethylhydrazines; D011073:Polyamines; D013096:Spermine; D000431:Ethanol; D013095:Spermidine; D011700:Putrescine