Concurrent unilateral chromatid damage and DNA strand breakage in response to 6-thioguanine treatment
dc.contributor.author | Fairchild, Craig R. | en_US |
dc.contributor.author | Maybaum, Jonathan | en_US |
dc.contributor.author | Kennedy, Katherine A. | en_US |
dc.date.accessioned | 2006-04-07T19:25:23Z | |
dc.date.available | 2006-04-07T19:25:23Z | |
dc.date.issued | 1986-10-15 | en_US |
dc.identifier.citation | Fairchild, Craig R., Maybaum, Jonathan, Kennedy, Katherine A. (1986/10/15)."Concurrent unilateral chromatid damage and DNA strand breakage in response to 6-thioguanine treatment." Biochemical Pharmacology 35(20): 3533-3541. <http://hdl.handle.net/2027.42/26014> | en_US |
dc.identifier.uri | http://www.sciencedirect.com/science/article/B6T4P-4777X31-1DH/2/6dbf6d81de971ee65399823057b49754 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/26014 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=3533081&dopt=citation | en_US |
dc.description.abstract | The delayed cytotoxicity of 6-thioguanine (TG) may relate to the arrest of cells in G2 upon completion of one cell cycle after drug exposure. In Chinese hamster ovary (CHO) cells, both the unilateral chromatid damage in G2 chromosomes, determined by induction of premature condensed chromosome condensation [Maybaum and Mandel, Cancer Res. 43, 3852 (1983)], and incorporation of TG into DNA resulting in DNA strand breakage [Christie et al., Cancer Res. 44, 3665 (1984)] were correlated with cytotoxicity. We have studied the correlation between strand breakage and unilateral chromatid damage in L1210 cells. DNA breaks were detected only when cells were treated with TG (0.25 [mu]M) for one cell cycle time (12 hr) followed by 12 hr in drug-free medium containing [3H]thymidine (TdR) to label the DNA. After simultaneous incubation of cells with drug and label during the first or second 12-hr period, strand breaks were not found. Strand breaks increased with dose, which correlated with greater cytotoxicity (0.01 to 0.25 [mu]M). Treatment of cells with 0.25 [mu]M TG for 12 hr, and transfer to drug-free medium for 12 hr prior to making prematurely condensed chromosomes (PCC), resulted in unilateral chromatid damage. Prominent curving of G2 chromosomes with gapping and diffuse staining of one of the sister chromatids occurred. The 4-fold increase in the percentage of cells in G2 compared with control cells suggested G2 arrest. When cells were treated with TG for 12 hr and PCC made immediately, neither the arrest of cells in G2 nor unilateral chromatid damage was observed. These data suggest that strand breaks and unilateral chromatid damage occur in the second cell cycle after TG exposure and that this damage may be important in TG-delayed cytotoxicity. | en_US |
dc.format.extent | 880658 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.language.iso | en_US | |
dc.publisher | Elsevier | en_US |
dc.title | Concurrent unilateral chromatid damage and DNA strand breakage in response to 6-thioguanine treatment | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Biological Chemistry | en_US |
dc.subject.hlbtoplevel | Science | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Department of Pharmacology, Upjohn Center for Clinical Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109, U.S.A. | en_US |
dc.contributor.affiliationother | Department of Pharmacology, The George Washington University, Washington, DC 20037, U.S.A. | en_US |
dc.contributor.affiliationother | Department of Pharmacology, The George Washington University, Washington, DC 20037, U.S.A. | en_US |
dc.identifier.pmid | 3533081 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/26014/1/0000081.pdf | en_US |
dc.identifier.doi | http://dx.doi.org/10.1016/0006-2952(86)90623-4 | en_US |
dc.identifier.source | Biochemical Pharmacology | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
Files in this item
Remediation of Harmful Language
The University of Michigan Library aims to describe library materials in a way that respects the people and communities who create, use, and are represented in our collections. Report harmful or offensive language in catalog records, finding aids, or elsewhere in our collections anonymously through our metadata feedback form. More information at Remediation of Harmful Language.
Accessibility
If you are unable to use this file in its current format, please select the Contact Us link and we can modify it to make it more accessible to you.