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.

Abstract

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.

• Authors: K Davis, D J Tomkins, A J Rainbow
• Journal: Somatic cell and molecular genetics (Somat Cell Mol Genet) Vol. 22 Issue 5 Pg. 393-402 (Sep 1996) ISSN: 0740-7750 [Print] United States
• PMID: 9039848 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA, Viral
• Cisplatin

Topics

• Adenoviruses, Human (drug effects, genetics, growth & development)
• Cell Line
• Cisplatin (pharmacology)
• Clone Cells
• Craniofacial Abnormalities (genetics, virology)
• DNA Replication (drug effects)
• DNA, Viral (biosynthesis)
• Fibroblasts (drug effects, virology)
• Growth Disorders (genetics, virology)
• Humans
• Limb Deformities, Congenital
• Syndrome
• Virus Activation (drug effects)