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

Molyneux, Gemma; Gibson, Frances M.; Gordon‐Smith, E. C.; Pilling, Andrew; Liu, Kai Chiu; Rizzo, Siân; Sulsh, Susan; Turton, John

doi:10.1111/j.0959-9673.2005.00452.x

Cited by 24 publications

(27 citation statements)

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“…Histological assessment of the spleen (Gibson et al 2003) demonstrated reduced haemopoietic activity in the red pulp, with only slight erythropoiesis, myelopoiesis and megakaryopoiesis. Furthermore, in a study with mitomycin in the mouse (Molyneux et al 2005), spleen relative weights were reduced to 50.6% of control at day 1 post-dosing, and here, histopathology showed a reduction in the cellularity of the red pulp (i.e. reduced haematopoiesis).…”

Section: Discussionmentioning

confidence: 51%

“…The second (theoretical) approach would involve the administration of a first BU regimen (ten doses, 9.0 mg/kg over 21 days), entry into the plateau phase from about day 50 post-dosing, followed by the administration of a second drug regimen, with a different agent, also known to induce late-stage/residual marrow injury. To identify such a second drug, investigations with CHB, MIT-C and azathioprine have been carried out (Molyneux et al 2004(Molyneux et al , 2005(Molyneux et al , 2008. Therefore, to progress to this second approach, the need has now arisen to develop a convenient shortterm method for identifying (i.e.…”

Section: Introductionmentioning

confidence: 99%

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Haemotoxicity of busulphan, doxorubicin, cisplatin and cyclophosphamide in the female BALB/c mouse using a brief regimen of drug administration

et al. 2010

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Many anticancer drugs are myelotoxic and cause bone marrow depression; however, generally, the marrow/blood returns to normal after treatment. Nevertheless, after the administration of some anti-neoplastic agents (e.g. busulphan, BU) under conditions as yet undefined, the marrow may begin a return towards normal, but normality may not be achieved, and late-stage/residual marrow injury may be evident. The present studies were conducted to develop a short-term mouse model (a 'screen') to identify late-stage/residual marrow injury using a brief regimen of drug administration. Female BALB/c mice were treated with BU, doxorubicin (DOX), cisplatin (CISPLAT) or cyclophosphamide (CYCLOPHOS) on days 1, 3 and 5. In 'preliminary studies', a maximum tolerated dose (MTD) for each drug was determined for use in 'main studies'. In main studies, mice were treated with vehicle (control), low and high (the MTD) dose levels of each agent. Necropsies were performed, and blood parameters and femoral/humeral nucleated marrow cell counts (FNCC/HNCC) were assessed on six occasions (from days 1 to 60/61 post-dosing). Late-stage/residual changes were apparent in BU-treated mice at day 61 post-dosing: RBC, Hb and haematocrit were reduced, mean cell volume/mean cell haemoglobin were increased and platelet and FNCC counts were decreased. Mice given DOX, CISPLAT and CYCLOPHOS, in general, showed no clear late-stage/residual effects (day 60/61). It was concluded that a brief regimen of drug administration, at an MTD, with assessment at day 60/61 post-dosing was a suitable short-term method/screen in the mouse for detecting late-stage/residual marrow injury for BU, a drug shown to exhibit these effects in man.

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Section: Discussionmentioning

confidence: 51%

Section: Introductionmentioning

confidence: 99%

Haemotoxicity of busulphan, doxorubicin, cisplatin and cyclophosphamide in the female BALB/c mouse using a brief regimen of drug administration

et al. 2010

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“…However, fever and weight loss were not induced in SFTSV-infected C57/BL6 mice (Table 1), and all tested mice survived. To evaluate if the immunocompromised animals could develop a more severe disease and even fatal outcome, we used immunosuppressive drug mitomycin C, which is known to inhibit the hematopoiesis in bone marrow (5), to treat SFTSV-infected mice. We found that with mitomycin C application, 50% of the SFTSV-infected mice died between day 9 and day 10, and the remaining surviving mice experienced a significant loss of body mass compared with uninfected mice administered mitomycin C in parallel (Fig.…”

Section: Resultsmentioning

confidence: 99%

Pathogenesis of emerging severe fever with thrombocytopenia syndrome virus in C57/BL6 mouse model

Jin

Liang

Ning

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

221

240

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The discovery of an emerging viral disease, severe fever with thrombocytopenia syndrome (SFTS), caused by SFTS virus (SFTSV), has prompted the need to understand pathogenesis of SFTSV. We are unique in establishing an infectious model of SFTS in C57/BL6 mice, resulting in hallmark symptoms of thrombocytopenia and leukocytopenia. Viral RNA and histopathological changes were identified in the spleen, liver, and kidney. However, viral replication was only found in the spleen, which suggested the spleen to be the principle target organ of SFTSV. Moreover, the number of macrophages and platelets were largely increased in the spleen, and SFTSV colocalized with platelets in cytoplasm of macrophages in the red pulp of the spleen. In vitro cellular assays further revealed that SFTSV adhered to mouse platelets and facilitated the phagocytosis of platelets by mouse primary macrophages, which in combination with in vivo findings, suggests that SFTSV-induced thrombocytopenia is caused by clearance of circulating virus-bound platelets by splenic macrophages. Thus, this study has elucidated the pathogenic mechanisms of thrombocytopenia in a mouse model resembling human SFTS disease.animal model | phlebovirus | pathology | reduction of platelets | macrophage infection S evere fever with thrombocytopenia syndrome (SFTS) is a recently identified emerging viral infectious disease in China that is caused by a novel phlebovirus in the family Bunyaviridae, SFTS virus (SFTSV) (1). Clinical features of SFTS patients include abrupt high fever, thrombocytopenia, leukocytopenia, and gastrointestinal symptoms. Laboratory tests commonly show elevated serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), lactate dehydrogenase, creatine kinase, creatine kinase MB fraction, as well as elongated activated partial-thromboplastin time (1). These abnormally changed laboratory parameters are indicative of the pathological lesions that occur in multiple organs and altered homeostasis of the coagulation systems of SFTS patients. Pathological studies of SFTS are absent because patient tissues are rarely donated after death in rural areas of China. Therefore, the causes of illness and death, as well as pathological changes within organs, remain unclear. To systematically investigate the pathogenic mechanisms of SFTS and understand key symptoms, such as thrombocytopenia, infectious animal models for SFTSV are urgently needed. ResultsEstablishment of a SFTSV Pathogenic Mouse Model. In our initial study, to identify an infectious animal model that could mimic most clinical features during SFTSV infection, the susceptibilities of three commonly used laboratory rodent strains for phlebovirus (2-4), C57/BL6 mice, BalB/C mice, and Syrian hamsters, were examined. The SFTSV strain HB29 was inoculated at 10 5 TCID 50 (50% tissue culture infective dose) per mouse or 5 × 10 5 TCID 50 per hamster through four different routes of infection, including intravenous, intramuscular, intraperitoneal, and intracerebral...

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“…Furthermore, some HUS animal models rely on the manipulation of the intestinal environment with different drugs such as antibiotics (Lindgren et al, 1993;Wadolkowski et al, 1990) or mitomycin C (Fujii et al, 1994) in order to establish reproducible infections. However, these treatments could disturb the immune response of the host (Domingo et al, 1995), alter Stx excretion (Grif et al, 1998) or induce microangiopathy (Molyneux et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Shiga toxin-producing Escherichia coli O157 : H7 shows an increased pathogenicity in mice after the passage through the gastrointestinal tract of the same host

Fernández-Brando

Miliwebsky

Mejias

et al. 2012

Journal of Medical Microbiology

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Haemolytic uraemic syndrome (HUS) is a rare but life-threatening complication of Shiga toxin (Stx)-producing Escherichia coli (STEC) infections, characterized by acute renal failure, thrombocytopenia and haemolytic anaemia. Although the main infection route is the consumption of contaminated food or water, person-to-person transmission has been suggested in several situations. Moreover, epidemiological data indicate that the horizontal transmission of several pathogens, including STEC, among individuals of the same species requires significantly lower doses than those used in animal models infected with laboratory-cultured bacteria. Thus, the aim of this study was to evaluate whether the passage of a clinically isolated STEC strain through the gastrointestinal tract of mice affects its pathogenicity in mice. To test this, weaned mice were orally inoculated by gavage with either an E. coli O157 : H7 isolate from an HUS patient, or the same strain recovered from stools after one or two successive passages through the gastrointestinal tract of the mice. We show that stool-recovered strains are able to induce a more generalized and persistent colonization than the parent strain. Furthermore, a 10 4 -fold-reduced inoculum of the stool-recovered strains still causes gut colonization and mouse mortality, which are not observed with the parent strain. These results indicate an increased pathogenicity in stoolrecovered strains that may be associated with an increased ability to colonize the mouse intestine.

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

Cited by 24 publications

References 65 publications

Haemotoxicity of busulphan, doxorubicin, cisplatin and cyclophosphamide in the female BALB/c mouse using a brief regimen of drug administration

Haemotoxicity of busulphan, doxorubicin, cisplatin and cyclophosphamide in the female BALB/c mouse using a brief regimen of drug administration

Pathogenesis of emerging severe fever with thrombocytopenia syndrome virus in C57/BL6 mouse model

Shiga toxin-producing Escherichia coli O157 : H7 shows an increased pathogenicity in mice after the passage through the gastrointestinal tract of the same host

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