In Vivo Micronucleus Assay in Mouse Bone Marrow

2019 ◽  
pp. 135-146
Author(s):  
Abhishek Kumar Jain ◽  
Alok Kumar Pandey
Keyword(s):  
Bone Marrow ◽  
Micronucleus Assay ◽  
Mouse Bone Marrow

scholarly journals O 6-Benzylguanine Potentiates the In Vivo Toxicity and Clastogenicity of Temozolomide and BCNU in Mouse Bone Marrow

Blood ◽  
1997 ◽  
Vol 89 (5) ◽  
pp. 1566-1573 ◽  
Author(s):  
Nachimuthu Chinnasamy ◽  
Joseph A. Rafferty ◽  
Ian Hickson ◽  
John Ashby ◽  
Helen Tinwell ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Antitumor Agents ◽  
Alkylating Agents ◽  
Micronucleus Assay ◽  
Hematological Toxicity ◽  
Mouse Bone Marrow ◽  
Macrophage Colony ◽  
Lower Magnitude ◽  
Marrow Cellularity

Abstract The effects of treatment of mice with O6-benzylguanine (O6-BeG) on the levels of O6-alkylguanine-DNA alkyltransferase (ATase) in the hematopoietic compartment and on the in vivo sensitivity of hematopoietic progenitor cells to the toxic and clastogenic effects of the antitumor agents 1,3-bis(2-chloroethyl)-nitrosourea (BCNU) and temozolomide were studied. When the overall effects of BCNU alone or with O6-BeG pretreatment were compared, dose potentiating factors of 4.17 for marrow cellularity, 4.57 for granulocyte macrophage-colony forming cells (GM-CFC) and 8.25 for colony forming unit-spleen (CFU-S) in O6-BeG pretreated versus nonpretreated animals were observed. A similar trend of dose potentiation was observed for temozolomide, although it was of lower magnitude: 1.20 for marrow cellularity, 1.63 for GM-CFC, and 1.68 for CFU-S. When the clastogenic effects of BCNU and temozolomide were examined in the mouse bone marrow micronucleus assay, a significantly (P < .05 to .001) higher frequency of micronuclei formation was observed in mice that received O6-BeG pretreatment compared with mice that received no pretreatment. These data suggest that the use of O6-BeG as a tumor-sensitizing agent before treatment of patients with O6-alkylating agents may lead to more severe hematological toxicity and possibly to an increased incidence of secondary leukemias as a result of elevated mutation frequencies in these patients.

scholarly journals O 6-Benzylguanine Potentiates the In Vivo Toxicity and Clastogenicity of Temozolomide and BCNU in Mouse Bone Marrow

Blood ◽  
1997 ◽  
Vol 89 (5) ◽  
pp. 1566-1573
Author(s):  
Nachimuthu Chinnasamy ◽  
Joseph A. Rafferty ◽  
Ian Hickson ◽  
John Ashby ◽  
Helen Tinwell ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Antitumor Agents ◽  
Alkylating Agents ◽  
Micronucleus Assay ◽  
Hematological Toxicity ◽  
Mouse Bone Marrow ◽  
Macrophage Colony ◽  
Lower Magnitude ◽  
Marrow Cellularity

The effects of treatment of mice with O6-benzylguanine (O6-BeG) on the levels of O6-alkylguanine-DNA alkyltransferase (ATase) in the hematopoietic compartment and on the in vivo sensitivity of hematopoietic progenitor cells to the toxic and clastogenic effects of the antitumor agents 1,3-bis(2-chloroethyl)-nitrosourea (BCNU) and temozolomide were studied. When the overall effects of BCNU alone or with O6-BeG pretreatment were compared, dose potentiating factors of 4.17 for marrow cellularity, 4.57 for granulocyte macrophage-colony forming cells (GM-CFC) and 8.25 for colony forming unit-spleen (CFU-S) in O6-BeG pretreated versus nonpretreated animals were observed. A similar trend of dose potentiation was observed for temozolomide, although it was of lower magnitude: 1.20 for marrow cellularity, 1.63 for GM-CFC, and 1.68 for CFU-S. When the clastogenic effects of BCNU and temozolomide were examined in the mouse bone marrow micronucleus assay, a significantly (P < .05 to .001) higher frequency of micronuclei formation was observed in mice that received O6-BeG pretreatment compared with mice that received no pretreatment. These data suggest that the use of O6-BeG as a tumor-sensitizing agent before treatment of patients with O6-alkylating agents may lead to more severe hematological toxicity and possibly to an increased incidence of secondary leukemias as a result of elevated mutation frequencies in these patients.

Expression of human adenosine deaminase in murine hematopoietic cells

1988 ◽  
Vol 8 (12) ◽  
pp. 5116-5125
Author(s):  
J W Belmont ◽  
G R MacGregor ◽  
K Wager-Smith ◽  
F A Fletcher ◽  
K A Moore ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Adenosine Deaminase ◽  
High Titer ◽  
Virus Production ◽  
Marrow Transplant ◽  
Mouse Bone Marrow ◽  
Regulation Of Expression ◽  
Murine Bone Marrow

Multiple replication-defective retrovirus vectors were tested for their ability to transfer and express human adenosine deaminase in vitro and in vivo in a mouse bone marrow transplantation model. High-titer virus production was obtained from vectors by using both a retrovirus long terminal repeat promoter and internal transcriptional units with human c-fos and herpes virus thymidine kinase promoters. After infection of primary murine bone marrow with one of these vectors, human adenosine deaminase was detected in 60 to 85% of spleen colony-forming units and in the blood of 14 of 14 syngeneic marrow transplant recipients. This system offers the opportunity to assess methods for increasing efficiency of gene transfer, for regulation of expression of foreign genes in hematopoietic progenitors, and for long-term measurement of the stability of expression in these cells.

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