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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.
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
html.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.


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