Abstract | BACKGROUND & AIMS: METHODS: Apoptotic and mitotic indices were measured in the small and large intestine on a cell positional basis at intervals throughout the 72-hour period after administration of 5-FU (40 mg/kg) and PDTC (250 mg/kg). The proportion of crypts regenerating after 5-FU (600-1200 mg/kg) and PDTC (500 mg/kg) was also measured. RESULTS:
5-FU therapy induces substantial apoptotic cell death with simultaneous inhibition of mitotic activity within the small and large intestinal epithelium. PDTC reduces 5-FU-induced apoptotic events in the colon by 49%, predominantly among clonogenic stem and transit cells while promoting the early recovery of mitotic activity. As a consequence, PDTC increased the proportion of regenerating colonic crypts after 5-FU therapy. PDTC did not, however, significantly modulate 5-FU toxicity in the small intestine. CONCLUSIONS:
PDTC does not augment the intestinal toxicity of 5-FU and actually protects the colonic mucosa. These results support further investigation of PDTC and related compounds as treatments for colorectal cancer.
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Authors | S P Bach, R Chinery, S T O'Dwyer, C S Potten, R J Coffey, A J Watson |
Journal | Gastroenterology
(Gastroenterology)
Vol. 118
Issue 1
Pg. 81-9
(Jan 2000)
ISSN: 0016-5085 [Print] United States |
PMID | 10611156
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Antimetabolites, Antineoplastic
- Antioxidants
- Pyrrolidines
- Thiocarbamates
- pyrrolidine dithiocarbamic acid
- Fluorouracil
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Topics |
- Animals
- Antimetabolites, Antineoplastic
(administration & dosage, toxicity)
- Antioxidants
(pharmacology)
- Apoptosis
(drug effects)
- Colon
(cytology, drug effects)
- Drug Interactions
- Fluorouracil
(administration & dosage, toxicity)
- Intestine, Small
(cytology, drug effects)
- Mice
- Mice, Inbred Strains
- Mitosis
(drug effects)
- Pyrrolidines
(pharmacology)
- Thiocarbamates
(pharmacology)
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