Busulfan-induced pathological changes of the cerebellar development in infant rats

Ohira, Toko; Andõ, Ryõ; Saito, Tsubasa; Yahata, Megumi; Oshima, Yosuke; Tamura, Kazutoshi

doi:10.1016/j.etp.2012.11.005

Cited by 6 publications

(9 citation statements)

References 32 publications

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“…These histopathological findings suggest that active cell proliferation occurs in the external granular layer on PD 6 in rats. It was reported that active cell proliferation is observed in the external granular layer by PD 13 in rats [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

“…Six-day-old male infant rats were treated with 1 mg/kg of MTX, and their brains were sampled from 1, 2, 3, 4, 8 and 15 days after treatment (DAT) to examine the time-course histopathological changes in the cerebellum. The specific timing of MTX administration we used was selected, because the injection of DNA- damaging chemicals such busulfan, on PD6 induced apoptosis in external granular cells of cerebellum [ 36 ]. In our preliminary study, MTX 0.1 mg/kg treatment induced few pathological changes, and MTX 0.5 mg/kg treatment induced quite mild pathological changes in the cerebellum.…”

Section: Methodsmentioning

confidence: 99%

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Effect of methotrexate on cerebellar development in infant rats

Sugiyama

Sun

Ueda

et al. 2015

The Journal of Veterinary Medical Science

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Six-day-old rats were treated intraperitoneal injections with methotrexate 1 mg/kg, and the cerebellum was examined. Both the length and width of the vermis decreased in the methotrexate-treated group instead of the control from 4 day after treatment (DAT) onward. A significant reduction in the width of the external granular layer was detected on 2 and 3 DAT in the methotrexate group. By 4 DAT, the width of the external granular layer of the methotrexate group was indistinguishable from the control, and by 8 DAT, it was greater than that of the control. The molecular layer of methotrexate group on 8 and 15 DAT was thinner than that of the control. On 1 DAT, in the methotrexate group, there were many TUNEL and cleaved caspase-3-positive granular cells throughout the external granular layer, and they decreased time-dependently. On 1 DAT, in the methotrexate group, phospho-histone H3-positive cells in the external granular layer were fewer than in the control and tended to increase on 2–4 DAT. The p21-positive-rate of the external granule cells in the MTX group was higher than in the control on 1–4 DAT. These results suggested that methotrexate exposure on postnatal day 6 induces a delay, slowing in the migration of external granular cells to the inner granular layer, attributed to decrease or inhibition in the production of external granular cells that had arisen from apoptosis and the decrease in cell proliferative activity, resulting in cerebellar hypoplasia.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Effect of methotrexate on cerebellar development in infant rats

Sugiyama

Sun

Ueda

et al. 2015

The Journal of Veterinary Medical Science

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“…As mentioned above, those in the CNS have been previously reported 19 , and those in the eyes will be published elsewhere in the near future.…”

Section: Discussionmentioning

confidence: 82%

“…It is also reported that busulfan induces histopathological changes in the lungs 8 , 9 , 10 , 11 in adult humans and in gastrointestinal tissues 12 , lymphoid tissues 13 and gonadal tissues 14 , 15 , 16 , 17 , 18 in adult rats. On the other hand, there are few reports of systemic histopathological changes in infant animals induced by busulfan except for our previous report of busulfan-induced CNS lesions in infant rats 19 .…”

Section: Introductionmentioning

confidence: 77%

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Systemic Histopathology of Infant Rats Exposed to Busulfan

et al. 2014

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Busulfan is an antineoplastic bifunctional alkylating agent. We previously reported the busulfan-induced systemic histopathological changes in fetal rats and the sequence of brain lesions in fetal and infant rats. In the present study, in order to clarify the nature and sequence of busulfan-induced systemic histopathological changes in infant rats, 6-day-old male infant rats were subcutaneously administered 20 mg/kg of busulfan and histopathologically examined at 1, 2, 4, 7 and 14 days after treatment (DAT). As a result, histopathological changes characterized by pyknosis of component cells were observed in the heart, lungs, stomach, intestines, liver, kidneys, testes, epididymides, hematopoietic and lymphoid tissues, dorsal skin and femur as well as in the brain and eyes (data not shown in this paper). Such pyknosis transiently appeared until 7 DAT with prominence at 2 and/or 4 DAT in each tissue, except for the thymus, in which pyknosis peaked at 1 DAT. Most of the pyknotic nuclei were immunohistochemically positive for cleaved caspase-3, indicating that pyknotic cells were apoptotic. Different from the reports of fetal and adult rats, apoptosis was also found in cardiomyocytes and osteoblasts in infant rats.

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Busulfan

Sarkar¹

2024

Encyclopedia of Toxicology

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Busulfan-induced pathological changes of the cerebellar development in infant rats

Cited by 6 publications

References 32 publications

Effect of methotrexate on cerebellar development in infant rats

Effect of methotrexate on cerebellar development in infant rats

Systemic Histopathology of Infant Rats Exposed to Busulfan

Busulfan

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