Gene-specific formation and repair of cisplatin intrastrand adducts and interstrand cross-links in Chinese hamster ovary cells

We have used three methods to study the formation and repair of intrastrand adducts and interstrand cross-links in the DNA of Chinese hamster ovary cells induced by the anticancer drug cis-diamminedichloroplatinum II (cisplatin). Using atomic absorption spectroscopy, we found that 21% of the total g...

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Bibliographic Details
Published in:The Journal of biological chemistry 1991-04, Vol.266 (11), p.7101-7107
Main Authors: Jones, J C, Zhen, W P, Reed, E, Parker, R J, Sancar, A, Bohr, V A
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Cell Line
Cisplatin - pharmacology
Cricetinae
Cricetulus
Cross-Linking Reagents
DNA - drug effects
DNA - isolation & purification
DNA Damage
DNA Repair
Female
Fundamental and applied biological sciences. Psychology
Genes
Molecular and cellular biology
Molecular genetics
Mutagenesis. Repair
Ovary
Proto-Oncogenes
Tetrahydrofolate Dehydrogenase - genetics
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Summary:We have used three methods to study the formation and repair of intrastrand adducts and interstrand cross-links in the DNA of Chinese hamster ovary cells induced by the anticancer drug cis-diamminedichloroplatinum II (cisplatin). Using atomic absorption spectroscopy, we found that 21% of the total genomic cisplatin adducts were removed at 8 h and 42% at 24 h. We used ABC excinuclease digestion, coupled with out previously reported methodology to quantify DNA in specific genomic regions. These adducts were removed faster in the transcribed dihydrofolate reductase and c-myc genes compared to a noncoding fragment, a region containing the little or nontranscribed c-fos oncogene, and to the overall genome. Interstrand cross-links in specific sequences were quantified by Southern hybridization of denatured-renatured DNA separated on a neutral gel. We found that cross-links were removed more efficiently from the gene regions than intrastrand adducts and, at high levels of cross-linking, removal was similar from transcribed and from nontranscribed regions.
ISSN:0021-9258
1083-351X
DOI:10.1016/S0021-9258(20)89616-1