Aging. Increased responsiveness of colorectal mucosa to carcinogen stimulation and protective role of folic acid.
Recent investigations have demonstrated a protective role for folic acid in dysplasia and neoplasia, through an unknown mechanism. The current study was designed to evaluate whether the protective role of folic acid is due, in part, to its antiproliferative properties. In addition, because colorectal neoplasia is more common with increasing age, we have compared results in both old (22 months) and young (3 months) rats. Colorectal mucosal explants of rats treated with the known carcinogen methylazoxymethanol, were supplemented with folic acid. Ornithine decarboxylase was then measured as an index of cellular proliferative activity. We observed that supplemental folic acid suppressed carcinogen-induced ornithine decarboxylase activity by 64% in the old and 74% in the young rats. Furthermore, a similar phenomenon was observed for tyrosine kinase, which was measured for comparison. The suppression of hyperproliferative activity by supplemental folic acid may contribute to the protective effect of folic acid in colorectal neoplasia.
Division of Gastroenterology, Henry Ford Hospital, Detroit, Michigan 48202.
Y M
YM
Nensey
F L
FL
Arlow
A P
AP
Majumdar
D000375:Aging / Q000187:drug effects* / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D003106:Colon / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology; D005492:Folic Acid / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008746:Methylazoxymethanol Acetate / Q000494:pharmacology*; D009924:Organ Culture Techniques; D009955:Ornithine Decarboxylase / Q000032:analysis / Q000187:drug effects; D010865:Pilot Projects; D011505:Protein-Tyrosine Kinases / Q000032:analysis / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D012007:Rectum / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology; D013047:Specific Pathogen-Free Organisms
D008746:Methylazoxymethanol Acetate; D005492:Folic Acid; D011505:Protein-Tyrosine Kinases; D009955:Ornithine Decarboxylase