Dosage time affects alkylating agents induced micronuclei in mouse peripheral blood reticulocytes through the function of erythropoietin
Autor: | Hiroyuki Sakakibara, Kayoko Shimoi, Shoji Masumori, Keiichi Itoh, Michiko T. Yasuda, Daisuke Mukai |
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Rok vydání: | 2019 |
Předmět: |
Male
medicine.medical_specialty Alkylating Agents Reticulocytes Light DNA damage Mitomycin bcl-X Protein Apoptosis Bone Marrow Cells 010501 environmental sciences Toxicology 030226 pharmacology & pharmacy 01 natural sciences Time 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Animals Cyclophosphamide Erythropoietin 0105 earth and related environmental sciences Mice Inbred C3H Chemistry Mitomycin C Methylnitrosourea Darkness Circadian Rhythm Comet assay Endocrinology medicine.anatomical_structure Vincristine Ethyl Methanesulfonate Micronucleus test Administration Metronomic Bone marrow Micronucleus Cell Nucleolus Ethylnitrosourea medicine.drug DNA Damage |
Zdroj: | The Journal of toxicological sciences. 44(4) |
ISSN: | 1880-3989 |
Popis: | Previously, we reported that the frequency of micronucleated reticulocytes (MNRETs) in the peripheral blood of male C3H/He mice intraperitoneally administered ethylnitrosourea (ENU) (25 mg/kg body weight) in the dark period (zeitgeber time, ZT15) was higher than in the light period (ZT3). In this study, to clarify the mechanism underlying this phenomenon, we investigated the differences in micronucleus (MN) induction observed between ZT3 and ZT15 using five chemicals, methylnitrosourea (MNU), ethylmethane sulfonate (EMS), mitomycin C, cyclophosphamide and vincristin. MNU and EMS, monofunctional alkylating agents, showed higher frequencies of MNRETs in the ZT15 than the ZT3 treatment similar to ENU. However, no differences were observed for the other chemicals. In the comet assay, more DNA damage was induced by ENU in the ZT15 than the ZT3 treatment. Furthermore, the plasma erythropoietin (EPO) level, a known effector of MN induction with anti-apoptotic activity mediated by Bcl-xL expression, was higher in the dark than in the light period. EPO did not increase the frequency of MNRETs. However, in the ENU treatment group at ZT3 following EPO injection a significant increase of MNRETs was observed similar to the ZT15 treatment. Higher expression of apoptosis-related genes such as Bcl-xL was induced in bone marrow cells from mice treated with ENU at ZT15 compared with ZT3. From these results, it was speculated that the differences in MN induction in the peripheral blood of mice exposed to monofunctional alkylating agents such as ENU depend on apoptotic or anti-apoptotic conditions related to the circadian rhythms of EPO in bone marrow. |
Databáze: | OpenAIRE |
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