title: High dietary niacin may increase prostaglandin formation but does not increase tumor formation in ApcMin/+ mice.
abstract: High doses of niacin (nicotinic acid) used to treat dyslipidemias cause flushing, due to high levels of prostaglandin D(2) (PGD(2)). GPR109A, a G-protein coupled receptor, triggers the flushing in the skin. In addition to boosting PGD(2), niacin binding to GPR109A activates the entire prostanoid cascade. We found that GPR109A occurs throughout the gastrointestinal tract. Mice that alternated between a 1% niacin diet and a control diet had higher urinary prostaglandin E(2) (PGE(2)) metabolite levels when on niacin (2.8-fold increase; 95% confidence interval, 1.8-3.9). PGE(2) promotes tumors in the intestines, whereas PGD(2) may have an opposite effect, on the basis of our report showing that transgenic hematopoietic prostaglandin D synthase suppresses intestinal adenomas in Apc(Min/+) mice. To determine if either tumor growth or tumor suppression prevails, we fed Apc(Min/+) mice a 1% niacin diet and assessed tumor development. A 1% niacin diet did not affect the number of tumors scored histologically in Apc(Min/+) mice at 14 wk (33 mice on niacin, 33 controls). Although niacin stimulates production of various prostaglandins, our results support an interpretation that very high intakes of niacin are safe in relation to intestinal tumors in this model.
authors.affiliation: Division of Medical Genetics, Department of Pediatrics, Harbor-UCLA Medical Center and Los Angeles Biomedical Research Institute, Torrance, California 90502, USA.
authors.forename: Alan M
authors.initials: AM
authors.lastname: Kwong
authors.forename: Brigette L
authors.initials: BL
authors.lastname: Tippin
authors.forename: Alicia M
authors.initials: AM
authors.lastname: Materi
authors.forename: Virgilio S
authors.initials: VS
authors.lastname: Buslon
authors.forename: Samuel W
authors.initials: SW
authors.lastname: French
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Lin
mesh_terms: D000236:Adenoma / Q000473:pathology; D000818:Animals; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D004032:Diet; D004305:Dose-Response Relationship, Drug; D005260:Female; D005483:Flushing; D006801:Humans; D007422:Intestines / Q000473:pathology; D019746:Intramolecular Oxidoreductases; D007535:Isomerases / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009369:Neoplasms / Q000473:pathology*; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology; D009525:Niacin / Q000008:administration & dosage*; D054510:Phospholipases A2, Cytosolic / Q000378:metabolism; D011453:Prostaglandins / Q000652:urine*; D012333:RNA, Messenger / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: C530105:Ccnd1 protein, mouse; C473652:Hcar2 protein, mouse; D011453:Prostaglandins; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D011978:Receptors, Nicotinic; D042461:Vascular Endothelial Growth Factor A; D019938:Cyclin D1; D009525:Niacin; D054510:Phospholipases A2, Cytosolic; D007535:Isomerases; D019746:Intramolecular Oxidoreductases; C545516:HPGDS protein, mouse