Effect of mitomycin C on bone marrow cells in mice.

Matsumoto, Kiyoshi; Furuya, Tsuyoshi; Tobe, Masuo

doi:10.2131/jts.9.51

Cited by 8 publications

(11 citation statements)

References 6 publications

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“…Benning et al (1991) administered single intraperitoneal doses of MMC (1.6 mg/kg) to adult CD-1 mice and studied erythropoietic cytotoxicity up to day 7 post-dosing. Matsumoto et al (1984) administered single intraperitoneal doses of MMC at 2.0 mg/kg to male ddY mice and studied marrow cell counts and peripheral blood reticulocytes at a series of time points up to day 11 post-dosing. Matsumoto et al (1984) administered single intraperitoneal doses of MMC at 2.0 mg/kg to male ddY mice and studied marrow cell counts and peripheral blood reticulocytes at a series of time points up to day 11 post-dosing.…”

Section: Discussionmentioning

confidence: 99%

“…With four doses administered over 8 days, the MTD was 2.5 mg/kg at 50 days post-dosing, and with eight doses given over 18 days, the MTD was also 2.5 mg/kg at 72 days post-dosing. In haematological studies, Benning et al (1991) used single intraperitoneal doses of 1.6 mg/kg in CD-1 mice; Kobayashi et al (1981) gave single doses of 6.0 mg/kg intraperitoneally to male CDF1 mice, and Matsumoto et al (1984) administered single intraperitoneal doses of 2.0 mg/kg MMC to male ddY mice. Bradner (1979) stated that the single-dose intraperitoneal LD 50 in male BDF1 mice was 7.5 mg/kg; Yamada (1960) gave the intraperitoneal LD 50 as 5.2 mg/kg.…”

Section: Discussionmentioning

confidence: 99%

“…Kobayashi et al (1981) gave single intraperitoneal doses of MMC at 6.0 mg/kg to male CD2F1 mice and studied bone marrow suppression up to day 7 post-dosing. Matsumoto et al (1984) administered single intraperitoneal doses of MMC at 2.0 mg/kg to male ddY mice and studied marrow cell counts and peripheral blood reticulocytes at a series of time points up to day 11 post-dosing. Bradner (1979) administered MMC at 7.5 mg/kg intraperitoneally to male BDF1 mice and studied changes in peripheral blood WBC up to day 7 post-dosing.…”

Section: Discussionmentioning

confidence: 99%

“…Philips et al (1960) reported the intraperitoneal single-dose LD 50 in male Swiss mice as 8.5 mg/kg; when five daily doses were administered, the LD 50 was 2.3 mg/kg. In haematological studies, Benning et al (1991) used single intraperitoneal doses of 1.6 mg/kg in CD-1 mice; Kobayashi et al (1981) gave single doses of 6.0 mg/kg intraperitoneally to male CDF1 mice, and Matsumoto et al (1984) administered single intraperitoneal doses of 2.0 mg/kg MMC to male ddY mice.…”

Section: Discussionmentioning

confidence: 99%

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The haemotoxicity of mitomycin in a repeat dose study in the female CD‐1 mouse

Molyneux

Gibson

Gordon‐Smith

et al. 2005

Int J Experimental Path

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Mitomycin (MMC), like many antineoplastic drugs, induces a predictable, dose-related, bone marrow depression in man and laboratory animals; this change is generally reversible. However, there is evidence that MMC may also cause a late-stage or residual bone marrow injury. The present study in female CD-1 mice investigated the haematological and bone marrow changes induced by MMC in a repeat dose study lasting 50 days. Control and MMC-treated mice were dosed intraperitoneally on eight occasions over 18 days with vehicle, or MMC at 2.5 mg/kg, autopsied (n = 6-12) at 1, 7, 14, 28, 42 and 50 days after the final dose and haematological changes investigated. Femoral nucleated bone marrow cell counts and levels of apoptosis were also evaluated and clonogenic assays carried out; serum levels of FLT3 ligand (FL) were assessed. At day 1 post-dosing, MMC induced significant reductions in RBC, Hb and haematocrit (HCT) values, and there were decreases in reticulocyte, platelet, and femoral nucleated cell counts (FNCC); neutrophil, lymphocyte and monocyte values were also significantly reduced. On days 7 and 14 post-dosing, all haematological parameters showed evidence of a return towards normal values, but at these times, and at day 28, values for RBC and FNCC remained significantly reduced in comparison with controls. At days 42 and 50 post-dosing, many haematological parameters in MMC-treated mice had returned to control levels; however, there remained evidence of late-stage effects on RBC, Hb and HCT values, and FNCC also continued to be significantly decreased. Results for granulocyte-macrophage colony-forming units and erythroid colonies showed a profound decrease immediately post-dosing, but a return to normal values was evident at day 50. Serum FL concentrations demonstrated very significant increases in the immediate post-dosing period, but a return to normal was seen at day 50 post-dosing; a relatively similar pattern was seen in the number of apoptotic femoral marrow nucleated cells. The histopathological examination of kidney tissues from MMC animals at day 42 and 50 post-dosing showed evidence of hydronephrosis with cortical glomerular/tubular atrophy and degeneration. It is therefore concluded that MMC administered on eight occasions over 18 days to female CD-1 mice at 2.5 mg/kg induced profound changes in haematological and bone marrow parameters in the immediate post-dosing period with a return to normal levels at day 50 post-dosing; however, there was evidence of mild but significant late-stage/residual effects on RBC and FNCC, and on cells of the erythroid lineage in the bone marrow.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

The haemotoxicity of mitomycin in a repeat dose study in the female CD‐1 mouse

Molyneux

Gibson

Gordon‐Smith

et al. 2005

Int J Experimental Path

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“…Whole-mount staining was carried out according to procedures described in the literature, with modifications. 18,22 Normal mouse buccal mucosa was fixed in 95% ethanol at room temperature for 60 min. Before peeling the epithelial sheets from the lamina propria, the tissue was soaked in a solution of Dispase I (386-02271; Fujifilm, Tokyo, Japan) at a concentration of 1000 PU/mL in PBS with 1.8 mM calcium (14040-133; Thermo Fisher Scientific) at 4 C overnight.…”

Section: Whole-mount Stainingmentioning

confidence: 99%

Zonula occludens‐1 distribution and barrier functions are affected by epithelial proliferation and turnover rates

et al. 2023

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Zonula occludens‐1 (ZO‐1) is a scaffolding protein of tight junctions, which seal adjacent epithelial cells, that is also expressed in adherens junctions. The distribution pattern of ZO‐1 differs among stratified squamous epithelia, including that between skin and oral buccal mucosa. However, the causes for this difference, and the mechanisms underlying ZO‐1 spatial regulation, have yet to be elucidated. In this study, we showed that epithelial turnover and proliferation are associated with ZO‐1 distribution in squamous epithelia. We tried to verify the regulation of ZO‐1 by comparing normal skin and psoriasis, known as inflammatory skin disease with rapid turnover. We as well compared buccal mucosa and oral lichen planus, known as an inflammatory oral disease with a longer turnover interval. The imiquimod (IMQ) mouse model, often used as a psoriasis model, can promote cell proliferation. On the contrary, we peritoneally injected mice mitomycin C, which reduces cell proliferation. We examined whether IMQ and mitomycin C cause changes in the distribution and appearance of ZO‐1. Human samples and mouse pharmacological models revealed that slower epithelial turnover/proliferation led to the confinement of ZO‐1 to the uppermost part of squamous epithelia. In contrast, ZO‐1 was widely distributed under conditions of faster cell turnover/proliferation. Cell culture experiments and mathematical modelling corroborated these ZO‐1 distribution patterns. These findings demonstrate that ZO‐1 distribution is affected by epithelial cell dynamics.

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Engraftment of Syngeneic and Allogeneic Endothelial Cells, Hepatocytes and Cholangiocytes Into Partially Hepatectomized Rats Previously Treated With Mitomycin C

Brilliant¹,

Mills²,

Callanan³

et al. 2009

Transplantation

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Background Pretreatment with retrorsine crosslinks host hepatocyte DNA and prevents proliferation after partial hepatectomy (PH), allowing selective expansion of transplanted progenitors. Shortcomings are length of protocol and carcinogenicity of retrorsine. Methods This report describes a rapid liver repopulation protocol using mitomycin C (MMC) to block proliferation of rat hepatocytes in response to PH. One week post-MMC treatment, dipeptidyl peptidase IV negative (DPPIV−) host rats were given a PH followed by injection of late gestation, newborn or adult total liver isolates from DPPIV+ rats. For allogeneic transplantation, host rats received injections of anti-CD3 antibody before and after PH. Results Host liver staining 2–9 weeks post-transplantation revealed well-defined donor hepatocyte colonies with strong canalicular DPPIV activity. At the same cell dose, fetal and newborn isolates produced more colonies than adult liver isolates. Hepatocyte colonies also co-expressed marker proteins characteristic of adult hepatocytes and showed polarized localization of plasma membrane proteins. Host livers contained large clusters of sinusoids lined by DPPIV+ endothelial cells co-expressing the endothelial cell marker, RECA-1 but lacked the canalicular marker leucine aminopeptidase. Colonies containing donor hepatocytes, endothelial cells and bile ducts, were also observed. Similar levels of engraftment and expansion were achieved with allogeneic liver cell isolates by using anti-CD3 antibody treatment. Conclusions The MMC transplantation model provides a rapid method for engraftment and expansion of hepatocytes, endothelial cells and cholangiocytes and should be applicable to investigations centering on the role of endothelial cells in liver regeneration and the identification and characterization of putative endothelial, hepatocyte and cholangiocyte progenitors.

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Effect of mitomycin C on bone marrow cells in mice.

Cited by 8 publications

References 6 publications

The haemotoxicity of mitomycin in a repeat dose study in the female CD‐1 mouse

The haemotoxicity of mitomycin in a repeat dose study in the female CD‐1 mouse

Zonula occludens‐1 distribution and barrier functions are affected by epithelial proliferation and turnover rates

Engraftment of Syngeneic and Allogeneic Endothelial Cells, Hepatocytes and Cholangiocytes Into Partially Hepatectomized Rats Previously Treated With Mitomycin C

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