Biomaterial Database

Camptothecin hypersensitivity in poly(adenosine diphosphate-ribose) polymerase-deficient cell lines. 1989

S Chatterjee, and M F Cheng, and D Trivedi, and S J Petzold, and N A Berger

Ireland Cancer Center, University Hospitals of Cleveland, Case Western Reserve University, OH 44106.

Mutant cell lines, derived from the Chinese hamster V79 cell line, deficient in poly(adenosine diphosphate-ribose) polymerase activity, and previously shown to be resistant to topoisomerase II inhibitors, were found to be hypersensitive to camptothecin, a topoisomerase I inhibitor. In all the cell lines, camptothecin induced dose-dependent protein-associated DNA single-strand breaks and sister chromatid exchanges. The increased sensitivity to camptothecin-induced cytotoxicity was not associated with an increase in DNA single strand breaks or sister chromatid exchanges. These results suggest the absence of any direct causal relation between (1) camptothecin induced sister chromatid exchanges and cytotoxicity or (2) camptothecin induced DNA strand breaks and cytotoxicity. The hypersensitivity of these mutant cell lines to camptothecin suggests that poly(adenosine diphosphate-ribose) polymerase is involved with topoisomerase I in modulating camptothecin induced cytotoxicity.

UI	MeSH Term	Description	Entries
D011065	Poly(ADP-ribose) Polymerases	Enzymes that catalyze the transfer of multiple ADP-RIBOSE groups from nicotinamide-adenine dinucleotide (NAD) onto protein targets, thus building up a linear or branched homopolymer of repeating ADP-ribose units i.e., POLY ADENOSINE DIPHOSPHATE RIBOSE.	ADP-Ribosyltransferase (Polymerizing),Poly ADP Ribose Polymerase,Poly(ADP-Ribose) Synthase,Poly(ADP-ribose) Polymerase,PARP Polymerase,Poly ADP Ribose Transferase,Poly ADP-Ribose Synthase,Poly(ADP-Ribose) Transferase,Poly(ADPR) Polymerase,Poly(ADPribose) Polymerase,Poly ADP Ribose Synthase,Polymerase, PARP,Synthase, Poly ADP-Ribose
D002166	Camptothecin	An alkaloid isolated from the stem wood of the Chinese tree, Camptotheca acuminata. This compound selectively inhibits the nuclear enzyme DNA TOPOISOMERASES, TYPE I. Several semisynthetic analogs of camptothecin have demonstrated antitumor activity.	Camptothecine
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell
D002470	Cell Survival	The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.	Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
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
D004277	DNA, Single-Stranded	A single chain of deoxyribonucleotides that occurs in some bacteria and viruses. It usually exists as a covalently closed circle.	Single-Stranded DNA,DNA, Single Stranded,Single Stranded DNA
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D006224	Cricetinae	A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.	Cricetus,Hamsters,Hamster
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
D012854	Sister Chromatid Exchange	An exchange of segments between the sister chromatids of a chromosome, either between the sister chromatids of a meiotic tetrad or between the sister chromatids of a duplicated somatic chromosome. Its frequency is increased by ultraviolet and ionizing radiation and other mutagenic agents and is particularly high in BLOOM SYNDROME.	Chromatid Exchange, Sister,Chromatid Exchanges, Sister,Exchange, Sister Chromatid,Exchanges, Sister Chromatid,Sister Chromatid Exchanges