The effect of dietary selenium deficiency on acute colorectal mucosal nucleotoxicity induced by several carcinogens in the rodent.
BACKGROUND
Selenium (SE) has been inversely associated with colon cancer risk. Two potential mechanisms of this effect were examined in a rodent short-term carcinogenesis assay: whether dietary SE deficiency altered the initiation aspect of carcinogenesis in the colon, and whether SE altered carcinogen metabolism.


METHODS
Animal laboratory.


METHODS
52 Sprague-Dawley rats, divided into a SE diet deficient group (0.002 parts per million; ppm) and a SE sufficient (0.2 ppm) group.


METHODS
Weight, serum SE concentration, and karryorhectic index (KI), which is a measure of acute carcinogen induced nuclear toxicity in the colonic mucosa.


METHODS
After three weeks of acclimation to the diets, eight animals from each dietary group were injected with one of the following: dimethylhydrazine (DMH), a colon specific carcinogen, its metabolite, methylazoxymethanol (MAM), or 0.9% sodium chloride. Twenty-four hours after injection the colons were removed, blood drawn, and the stained colons assayed for nuclear aberrations.


RESULTS
No weight differences were generated by the dietary variations. Low-dietary SE resulted in serum SE declining markedly in the study period to 6 ng/ml versus 33 ng/ml in the SE sufficient group. Diet alone, and variations in weight gain, did not alter the KI. Both carcinogens greatly increased the KI in both the left and right colon. A SE-deficient diet was associated with a higher KI in both carcinogen groups in the right colon, with statistical significance for both the left and right colon in the MAM injection group.


CONCLUSIONS
Dietary SE deficiency is associated with increased KI of the colon in MAM treated rats. SE, therefore, has a protective effect in the initiation phase of carcinogenesis.
Nelson
R L
RL
Department of Surgery, University of Illinois College of Medicine at Chicago, USA.
Abcarian
H
H
Nelson
T M
TM
Misumi
A
A
Kako
H
H
Rizk
S
S
Sky-Peck
H
H
D000818:Animals; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000633:toxicity*; D015179:Colorectal Neoplasms / Q000139:chemically induced* / Q000473:pathology; D003677:Deficiency Diseases / Q000503:physiopathology; D004195:Disease Models, Animal; D007413:Intestinal Mucosa; D008297:Male; D008746:Methylazoxymethanol Acetate / Q000031:analogs & derivatives / Q000633:toxicity; D008938:Mitosis / Q000187:drug effects; D009002:Monomethylhydrazine / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012643:Selenium / Q000172:deficiency*; D014410:Tumor Stem Cell Assay
D002273:Carcinogens; D008746:Methylazoxymethanol Acetate; D012643:Selenium; C030667:methylazoxymethanol; D009002:Monomethylhydrazine