Abnormal ultraviolet mutagenic spectrum in plasmid DNA replicated in cultured fibroblasts from a patient with the skin cancer-prone disease, xeroderma pigmentosum.

Abstract

A shuttle vector plasmid, pZ189, was utilized to assess the types of mutations that cells from a patient with xeroderma pigmentosum, complementation group D, introduce into ultraviolet (UV) damaged, replicating DNA. Patients with xeroderma pigmentosum have clinical and cellular UV hypersensitivity, increased frequency of sun-induced skin cancer, and deficient DNA repair. In comparison to UV-treated pZ189 replicated in DNA repair-proficient cells, there were fewer surviving plasmids, a higher frequency of plasmids with mutations, fewer plasmids with two or more mutations in the marker gene, and a new mutagenic hotspot. The major type of base substitution mutation was the G:C to A:T transition with both cell lines. These results, together with similar findings published earlier with cells from a xeroderma pigmentosum patient in complementation group A, suggest that isolated G:C to A:T somatic mutations may be particularly important in generation of human skin cancer by UV radiation.

• Authors: S Seetharam, M Protić-Sabljić, M M Seidman, K H Kraemer
• Journal: The Journal of clinical investigation (J Clin Invest) Vol. 80 Issue 6 Pg. 1613-7 (Dec 1987) ISSN: 0021-9738 [Print] United States
• PMID: 3680516 (Publication Type: Journal Article)

Chemical References

• DNA

Topics

• Cell Line
• DNA (radiation effects)
• DNA Damage
• DNA Replication
• Female
• Humans
• Mutation
• Plasmids (radiation effects)
• Radiation Genetics
• Ultraviolet Rays
• Xeroderma Pigmentosum (genetics)