Target cells for the cytotoxic effects of carcinogens in the murine small bowel.

2.50
Hdl Handle:
http://hdl.handle.net/10541/109025
Title:
Target cells for the cytotoxic effects of carcinogens in the murine small bowel.
Authors:
Li, Y Q; Fan, Chun-Yang; O'Connor, Peter J; Winton, D J; Potten, Christopher S
Abstract:
Two direct-acting mutagens, N-nitroso-N-methylurea (NMU) and N-nitroso-N-ethylurea (NEU), and two agents requiring metabolic activation, 1-2-dimethylhydrazine (DMH) and N-nitrosodimethylamine (NDMA), were administered i.p. to mice. Sections of crypts of the small intestine were assayed for acute histological cell death at various times up to 12 h after treatment. Dead or dying cells exhibited the typical light microscopic morphological features of apoptosis. The incidence of apoptosis at each cell position along the side of longitudinal crypt sections was recorded and frequency plots of the incidence against cell position were determined. NEU (50 mg/kg) produced the highest incidence of cell death but this was closely followed by NDMA (50 mg/kg) and NMU (200 mg/kg). DMH (40 or 80 mg/kg) was the least cytotoxic but even here significantly elevated levels of cell death were observed. The highest incidence of cell death occurred 4-5 h after treatment with NEU, NMU and DMH and at 6 h after NDMA. The data obtained at 4 h after NEU suggest that approximately 22 cells out of a total crypt population of 250 cells are killed, but that for some cell positions near the crypt base (stem cell regions) up to 24% of the cells may be killed. Analysis of the changing shape of the frequency plots with time after treatment enabled the target cell position in the crypts for cytotoxicity to be estimated. This was at cell position 4 for NEU, NMU and DMH and at cell position 5 for NDMA. The stem cells in the crypts are believed to be located at the fourth cell position and hence at least NEU, NMU and DMH are targeting the stem cells with some specificity.
Affiliation:
CRC Department of Epithelial Biology, Paterson Institute for Cancer Research, Christie Hospital, Manchester, UK.
Citation:
Target cells for the cytotoxic effects of carcinogens in the murine small bowel. 1992, 13 (3):361-8 Carcinogenesis
Journal:
Carcinogenesis
Issue Date:
Mar-1992
URI:
http://hdl.handle.net/10541/109025
DOI:
10.1093/carcin/13.3.361
PubMed ID:
1547525
Type:
Article
Language:
en
ISSN:
0143-3334
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorLi, Y Qen
dc.contributor.authorFan, Chun-Yangen
dc.contributor.authorO'Connor, Peter Jen
dc.contributor.authorWinton, D Jen
dc.contributor.authorPotten, Christopher Sen
dc.date.accessioned2010-08-04T09:29:00Z-
dc.date.available2010-08-04T09:29:00Z-
dc.date.issued1992-03-
dc.identifier.citationTarget cells for the cytotoxic effects of carcinogens in the murine small bowel. 1992, 13 (3):361-8 Carcinogenesisen
dc.identifier.issn0143-3334-
dc.identifier.pmid1547525-
dc.identifier.doi10.1093/carcin/13.3.361-
dc.identifier.urihttp://hdl.handle.net/10541/109025-
dc.description.abstractTwo direct-acting mutagens, N-nitroso-N-methylurea (NMU) and N-nitroso-N-ethylurea (NEU), and two agents requiring metabolic activation, 1-2-dimethylhydrazine (DMH) and N-nitrosodimethylamine (NDMA), were administered i.p. to mice. Sections of crypts of the small intestine were assayed for acute histological cell death at various times up to 12 h after treatment. Dead or dying cells exhibited the typical light microscopic morphological features of apoptosis. The incidence of apoptosis at each cell position along the side of longitudinal crypt sections was recorded and frequency plots of the incidence against cell position were determined. NEU (50 mg/kg) produced the highest incidence of cell death but this was closely followed by NDMA (50 mg/kg) and NMU (200 mg/kg). DMH (40 or 80 mg/kg) was the least cytotoxic but even here significantly elevated levels of cell death were observed. The highest incidence of cell death occurred 4-5 h after treatment with NEU, NMU and DMH and at 6 h after NDMA. The data obtained at 4 h after NEU suggest that approximately 22 cells out of a total crypt population of 250 cells are killed, but that for some cell positions near the crypt base (stem cell regions) up to 24% of the cells may be killed. Analysis of the changing shape of the frequency plots with time after treatment enabled the target cell position in the crypts for cytotoxicity to be estimated. This was at cell position 4 for NEU, NMU and DMH and at cell position 5 for NDMA. The stem cells in the crypts are believed to be located at the fourth cell position and hence at least NEU, NMU and DMH are targeting the stem cells with some specificity.en
dc.language.isoenen
dc.subject.mesh1,2-Dimethylhydrazine-
dc.subject.meshAnimals-
dc.subject.meshDimethylhydrazines-
dc.subject.meshDimethylnitrosamine-
dc.subject.meshEthylnitrosourea-
dc.subject.meshFemale-
dc.subject.meshIntestine, Small-
dc.subject.meshMale-
dc.subject.meshMethylnitrosourea-
dc.subject.meshMice-
dc.subject.meshStem Cells-
dc.titleTarget cells for the cytotoxic effects of carcinogens in the murine small bowel.en
dc.typeArticleen
dc.contributor.departmentCRC Department of Epithelial Biology, Paterson Institute for Cancer Research, Christie Hospital, Manchester, UK.en
dc.identifier.journalCarcinogenesisen
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