Suppression of colorectal oncogenesis by selenium-enriched milk proteins: apoptosis and K-ras mutations.
The chemical form and bioavailability of dietary selenium may influence its protectiveness against colorectal cancer. Selenium is readily incorporated into milk proteins by feeding cows with selenized-yeast. This study examined whether a dairy source of organic selenium (as milk proteins) is more effective than a yeast source at inhibiting oncogenesis in carcinogen-treated mice and whether it regulates the homeostatic response to carcinogen-induced DNA damage. Dietary interventions are as follows: selenium-enriched milk protein isolate (Tatura-Bio Se; 0.5 or 1 ppm selenium) or milk protein control and selenized-yeast (Sel-Plex; 1 or 4 ppm selenium) with casein or casein alone as control. After 4 weeks on diet, mice received a single azoxymethane (10 mg/kg) injection to induce mutations and were killed 6 hours later. Measures were as follows: plasma selenium, cell proliferation, and acute apoptotic response to azoxymethane (AARGC). Separate groups of mice on the same diets were given 4 weekly azoxymethane (15 mg/kg) injections to induce oncogenesis. Mice were killed 6 or 30 weeks after the last azoxymethane injection. Measures were as follows: aberrant crypt foci (ACF), cancers, and K-ras mutations. Dairy-selenium at 1 ppm significantly suppressed ACF and cancers, whereas yeast-selenium at an equivalent selenium intake had no effect. Dairy-selenium significantly increased plasma selenium levels and AARGC, and reduced cell proliferation and frequency of K-ras mutations in ACF relative to an equivalent dose of selenium from yeast. Selenium-enriched milk protein isolate is superior to selenized-yeast in terms of its bioavailability and capacity to suppress oncogenesis. Suppression may be a consequence of enhanced apoptotic deletion of azoxymethane-induced DNA lesions and the subsequent reduction in frequency of K-ras mutations.
Hu
Ying
Y
Department of Medicine, Flinders Cancer Control Alliance, Flinders University of South Australia, Adelaide, Australia. ying.hu@flinders.edu.au
McIntosh
Graeme H
GH
Le Leu
Richard K
RK
Woodman
Richard
R
Young
Graeme P
GP
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001397:Azoxymethane; D002273:Carcinogens; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000473:pathology* / Q000517:prevention & control*; D004249:DNA Damage; D004032:Diet; D004305:Dose-Response Relationship, Drug; D011905:Genes, ras / Q000235:genetics*; D005979:Glutathione Peroxidase / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008894:Milk Proteins / Q000008:administration & dosage*; D009154:Mutation / Q000235:genetics*; D012643:Selenium / Q000008:administration & dosage* / Q000097:blood; D015003:Yeasts
D002273:Carcinogens; D008894:Milk Proteins; D005979:Glutathione Peroxidase; D012643:Selenium; D001397:Azoxymethane