title: [Diamine oxidase as blood biomarker in rats and humans to GI tract toxicity of fluorouracil anti-cancer drugs].
abstract: Diarrhea is a side effect of a 5-fluorouracil (5-FU) anti-cancer drug-induced intestinal mucosal disorder, which sometimes becomes more severe. Blood diamine oxidase (DAO; EC1. 4. 3. 6) activity is reported to be significantly correlated with activity in the small intestinal mucosal tissue, and to be a reliable indicator of small intestinal mucosal integrity and maturity. Here, we investigated whether blood DAO activity can be a biomarker for the gastrointestinal (GI) mucosal disorder caused by 5-FU anti-cancer drugs, both in rats and humans. From results of the rat study, the degree of jejunal mucosal disorder caused by the 5-FU anti-cancer drug was well correlated with a decrease in blood DAO activity. Clinically, 12 out of 28 patients (43%) administered 5-FU anti-cancer drug suffered from diarrhea. The plasma DAO activity within one week of the onset of diarrhea significantly decreased compared with that before the administration. Furthermore, before drug administration, plasma DAO activity in patients suffering from diarrhea was higher than those in patients without diarrhea. Although DAO activity differs by the individual, it is a useful biomarker for estimating the degree of intestinal mucosal disorder, and possibly for estimating manifestations of diarrhea induced by 5-FU anti-cancer drug administration.
authors.affiliation: Dept. of Digestive Apparatus Surgery, Showa University, Fujigaoka Hospital.
authors.forename: Tetsuhiro
authors.initials: T
authors.lastname: Goto
authors.forename: Taketo
authors.initials: T
authors.lastname: Matsubara
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Yoshizawa
authors.forename: Shouji
authors.initials: S
authors.lastname: Sasaya
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nemoto
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Sanada
authors.forename: Kenji
authors.initials: K
authors.lastname: Moriyama
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Kouchi
mesh_terms: D000368:Aged; D006631:Amine Oxidase (Copper-Containing) / Q000097:blood*; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects* / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D003967:Diarrhea / Q000097:blood* / Q000139:chemically induced; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects* / Q000627:therapeutic use; D005767:Gastrointestinal Diseases / Q000097:blood* / Q000139:chemically induced; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D051381:Rats
chemical_list: D000964:Antimetabolites, Antineoplastic; D015415:Biomarkers; D006631:Amine Oxidase (Copper-Containing); D005472:Fluorouracil