Fanconi anemia group A and D cell lines respond normally to inhibitors of cell cycle regulation.
Cells from patients with Fanconi anemia (FA) show decreased viability and decreased chromosome stability after treatment with DNA cross-linking agents, compared to normal cells. FA cells also show a relative accumulation at the G2/M transition after such treatment. This has suggested a possible checkpoint abnormality. In the studies presented here, treatment with hydroxyurea, caffeine or inhibitors of cell cycle kinases did not reveal abnormalities in survival or chromosome stability in FA-A or FA-D cells. Chromosomal breaks introduced by hydrogen peroxide or methyl methanesulfonate accumulated to the same extent in FA-A or FA-D cells as in normal cells. We conclude that FA-A and FA-D cells respond normally to agents known to alter the cell cycle or introduce DNA strand breaks. FA cells process strand breaks and a variety of DNA monoadducts normally. Our results are compatible with repair of DNA crosslinks being slower in FA than in normal cells and FA cells having normal cell cycle checkpoints.
Johnstone
P
P
Department of Molecular and Medical Genetics, Oregon Health Sciences University, Portland 97201, USA.
Reifsteck
C
C
Kohler
S
S
Worland
P
P
Olson
S
S
Moses
R E
RE
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects*; D002478:Cells, Cultured / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D019457:Chromosome Breakage; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D018736:DNA Adducts; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005199:Fanconi Anemia / Q000235:genetics / Q000473:pathology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006918:Hydroxyurea / Q000494:pharmacology; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D016685:Mitomycin / Q000494:pharmacology; D016877:Oxidants / Q000494:pharmacology
D000903:Antibiotics, Antineoplastic; D018906:Antineoplastic Agents, Alkylating; D000697:Central Nervous System Stimulants; D003432:Cross-Linking Reagents; D018736:DNA Adducts; D004791:Enzyme Inhibitors; D016877:Oxidants; D002110:Caffeine; D016685:Mitomycin; D008741:Methyl Methanesulfonate; D006861:Hydrogen Peroxide; D006918:Hydroxyurea