Roberts syndrome fibroblasts showing cisplatin hypersensitivity have normal host cell reactivation of cisplatin-treated adenovirus and normal capacity of cisplatin-treated cells for adenovirus DNA synthesis.
Roberts syndrome (RS) is a rare, recessively inherited disorder characterized by growth retardation, limb reductions and craniofacial deformities. Cells from a subset of afflicted individuals, termed RS+, display unusual separation or puffing of the heterochromatic regions of their chromosomes and are hypersensitive to several DNA-damaging agents including mitomycin C (MMC) and cisplatin, both of which can induce interstrand crosslinks in DNA. For this reason, we have investigated the ability of RS+ fibroblasts to repair cisplatin-induced DNA lesions using adenoviris as a probe. Host cell reactivation of cisplatin-treated adenovirus (Ad) was significantly reduced in nucleotide excision repair (NER)-deficient xeroderma pigmentosum (XP) cells but was normal in the two RS+ fibroblast strains and the Fanconi's anemia (FA)fibroblast strain tested. The capacity of cisplatin-treated cells for Ad DNA synthesis was reduced in XP and FA cells compared to normal human cells, but was not reduced in RS+ cells. These results indicate that the hypersensitivity of RS+ cells to cisplatin is not due to a deficiency in NER nor due to a deficiency in the pathway which leads to cisplatin hypersensitivity in FA cells. It is possible that the abnormal heterochromatin organisation of RS+ cells selectively renders the heterochromatic regions of the genome more susceptible to mutagen damage and/or less available for repair.
Davis
K
K
Department of Biology, McMaster University, Hamilton, Ontario, Canada.
Tomkins
D J
DJ
Rainbow
A J
AJ
D000260:Adenoviruses, Human / Q000187:drug effects / Q000235:genetics / Q000254:growth & development*; D002460:Cell Line; D002945:Cisplatin / Q000494:pharmacology*; D002999:Clone Cells; D019465:Craniofacial Abnormalities / Q000235:genetics* / Q000821:virology; D004261:DNA Replication / Q000187:drug effects*; D004279:DNA, Viral / Q000096:biosynthesis; D005347:Fibroblasts / Q000187:drug effects* / Q000821:virology; D006130:Growth Disorders / Q000235:genetics* / Q000821:virology; D006801:Humans; D017880:Limb Deformities, Congenital; D013577:Syndrome; D014775:Virus Activation / Q000187:drug effects*
D004279:DNA, Viral; D002945:Cisplatin