The effects of parathyroid hormone fragments on bone formation and their lack of effects on the initiation of colon carcinogenesis in rats as indicated by preneoplastic aberrant crypt formation.
The parathyroid hormone (PTH) and some of its fragments and analogs stimulate bone growth in various animal models and humans and one of them (hPTH-(1-34)) has been approved by the USFDA for treating osteoporosis. However, there are reports that PTH can stimulate the PI-3 kinase/mitogen-activated protein kinases-mediated proliferation of rat enterocytes and that primary hyperparathyroidism in humans is associated with an increased incidence of colon cancer. Here we have investigated the ability of two PTH fragments, hPTH-(1-34)NH(2) and [Leu(27)]cyclo(Glu(22)-Lys(26))hPTH-(1-31)NH(2) to initiate colon carcinogenesis or increase the initiatory activity of the widely used colon carcinogen azoxymethane (AOM). The initiation of colon carcinogenesis by AOM was indicated by the very early appearance of aberrant crypt foci. While both PTH peptides strongly stimulated femoral bone formation, they did not cause the appearance of ACFs or affect the number or the distribution along the colon of AOM-induced ACFs. Nor did AOM affect the PTHs' ability to stimulate bone formation. Thus, a relatively short PTH treatment that is long enough to strongly stimulate bone formation does not initiate colon carcinogenesis in rats.
Institute for Biological Sciences, National Research Council of Canada, Building M-54, Montreal Road Campus, Ottawa, Ontario K1A 0R6, Canada. pthosteo@rogers.com
James
J
Whitfield
Ranjana P
RP
Bird
Paul
P
Morley
Gordon E
GE
Willick
Jean-René
JR
Barbier
Susanne
S
MacLean
Virginia
V
Ross
D000818:Animals; D001397:Azoxymethane; D002273:Carcinogens; D003110:Colonic Neoplasms / Q000139:chemically induced*; D010012:Osteogenesis; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010446:Peptide Fragments; D011230:Precancerous Conditions / Q000139:chemically induced*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002273:Carcinogens; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D001397:Azoxymethane