Biomaterial Database

Progressive formation of DNA lesions in cultured Ehrlich ascites tumor cells treated with hydroxyurea. 1987

J C Li, and E Kaminskas

We have previously demonstrated an accumulation of strand breaks in mature DNA of cultured Ehrlich ascites tumor cells treated with methotrexate. We postulated that the strand breaks arose from unrepaired spontaneous DNA lesions. The present study describes a progressive accumulation of strand breaks in mature DNA of Ehrlich ascites cells treated with hydroxyurea (HU). Strand breaks were determined by alkaline elution. Accumulation of strand breaks was dependent on the length of incubation (0-16 h) and on HU concentration (0-10 mM). About 70% of strand breaks were repaired when cells were incubated without HU. About 67% of strand breaks were prevented by 0.4 mM deoxyadenosine, deoxyguanosine, and deoxycytidine, with or without thymidine. Prevention was less effective by deoxyadenosine and deoxyguanosine and ineffective by deoxycytidine. Free radical scavengers did not prevent strand breaks. S-phase cells accumulated about twice the number of strand breaks as non-S-phase cells. Cell survival decreased in proportion to the increase in HU concentration (0-10 mM). The results demonstrate that lack of purine, as well as of pyrimidine, nucleotides results in strand breaks in mature DNA, suggest that HU cytotoxicity is due to fragmentation of mature DNA, and caution against the use of HU in DNA repair studies.

UI	MeSH Term	Description	Entries
D002286	Carcinoma, Ehrlich Tumor	A transplantable, poorly differentiated malignant tumor which appeared originally as a spontaneous breast carcinoma in a mouse. It grows in both solid and ascitic forms.	Ehrlich Ascites Tumor,Ascites Tumor, Ehrlich,Ehrlich Tumor Carcinoma,Tumor, Ehrlich Ascites
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell
D003853	Deoxyribonucleosides	A purine or pyrimidine base bonded to DEOXYRIBOSE.
D003854	Deoxyribonucleotides	A purine or pyrimidine base bonded to a DEOXYRIBOSE containing a bond to a phosphate group.	Deoxyribonucleotide
D004247	DNA	A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).	DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D004249	DNA Damage	Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.	DNA Injury,DNA Lesion,DNA Lesions,Genotoxic Stress,Stress, Genotoxic,Injury, DNA,DNA Injuries
D004260	DNA Repair	The removal of DNA LESIONS and/or restoration of intact DNA strands without BASE PAIR MISMATCHES, intrastrand or interstrand crosslinks, or discontinuities in the DNA sugar-phosphate backbones.	DNA Damage Response
D006918	Hydroxyurea	An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase.	Hydroxycarbamid,Hydrea,Oncocarbide
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D012264	Ribonucleotide Reductases		Ribonucleotide Reductase,Reductase, Ribonucleotide,Reductases, Ribonucleotide