title: Issues of normal tissue toxicity in patient and animal studies--effect of carbogen breathing in rats after 5-fluorouracil treatment.
abstract: Non-invasive magnetic resonance spectroscopy (MRS) can be used in the clinic to monitor the pharmacokinetics of the chemotherapeutic drug 5-fluorouracil (5-FU) and the effects of modifiers. We report two studies of 5-FU toxicity in normal tissue--one with patients and the other an animal study. 1) 19F MRS signals from fluoronucleotides, cytotoxic anabolites of 5-FU metabolism, were observed in the livers of two patients treated with 5-FU for colorectal cancer, shown by computed tomography (CT) and ultrasound (US) to have no liver metastases. This is the first report of non-invasive monitoring of toxic 5-FU metabolites in normal human tissues. 2) In animals, carbogen-breathing enhances tumour uptake and the efficacy of 5-FU, and the method is under trial in patients. This study demonstrates that there were no significant effects of carbogen breathing on the levels of 5-FU and its metabolites in normal rat tissues, or on the histology of the tissues assessed after treatment.
authors.affiliation: Department of Biochemistry and Immunology, St. George's Hospital Medical School, London, UK.
authors.forename: J R
authors.initials: JR
authors.lastname: Griffiths
authors.forename: D J
authors.initials: DJ
authors.lastname: McIntyre
authors.forename: F A
authors.initials: FA
authors.lastname: Howe
authors.forename: P M
authors.initials: PM
authors.lastname: McSheehy
authors.lastname: Ojugo ASE
authors.forename: L M
authors.initials: LM
authors.lastname: Rodrigues
authors.forename: P
authors.initials: P
authors.lastname: Wadsworth
authors.forename: N M
authors.initials: NM
authors.lastname: Price
authors.forename: F
authors.initials: F
authors.lastname: Lofts
authors.forename: G
authors.initials: G
authors.lastname: Nicholson
authors.forename: K
authors.initials: K
authors.lastname: Smid
authors.forename: P
authors.initials: P
authors.lastname: Noordhuis
authors.forename: G J
authors.initials: GJ
authors.lastname: Peters
authors.forename: M
authors.initials: M
authors.lastname: Stubbs
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000532:radiotherapy / Q000556:secondary / Q000601:surgery; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D001682:Biological Availability; D001853:Bone Marrow / Q000737:chemistry / Q000648:ultrastructure; D002245:Carbon Dioxide / Q000494:pharmacology*; D002295:Carcinoma, Transitional Cell; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000601:surgery; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000378:metabolism; D003131:Combined Modality Therapy; D017809:Fatal Outcome; D005260:Female; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics*; D005468:Fluorodeoxyuridylate / Q000032:analysis; D005472:Fluorouracil / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000633:toxicity; D006801:Humans; D007421:Intestine, Small / Q000737:chemistry / Q000648:ultrastructure; D002955:Leucovorin / Q000627:therapeutic use; D008099:Liver / Q000737:chemistry / Q000000981:diagnostic imaging / Q000648:ultrastructure; D008113:Liver Neoplasms / Q000556:secondary; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D009378:Neoplasms, Multiple Primary; D010100:Oxygen / Q000494:pharmacology*; D051381:Rats; D011920:Rats, Inbred WF; D012811:Sigmoid Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery; D014057:Tomography, X-Ray Computed; D014463:Ultrasonography; D001749:Urinary Bladder Neoplasms
chemical_list: D000964:Antimetabolites, Antineoplastic; D005462:Fluorine Radioisotopes; D005468:Fluorodeoxyuridylate; D002245:Carbon Dioxide; C011700:carbogen; D002955:Leucovorin; D010100:Oxygen; D005472:Fluorouracil