Relative susceptibilities of XPA knockout mice and their heterozygous and wild-type littermates to UVB-induced skin cancer

Although xeroderma pigmentosum (XP) patients are rare, carriers of XP genes (heterozygotes) are much more common. Whether such carriers have an increased skin cancer risk is unknown. Recently developed mouse models for XP have opened up the possibility of determining the skin cancer risk of heterozy...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1997-02, Vol.57 (4), p.581-584
Main Authors: BERG, R. J. W, DE VRIES, A, VAN STEEG, H, DE GRUIJL, F. R
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Carcinoma, Squamous Cell - genetics
Carcinoma, Squamous Cell - pathology
Dermatology
Disease Susceptibility
Genotype
Medical sciences
Mice
Mice, Hairless
Mice, Knockout - genetics
Neoplasms, Radiation-Induced - genetics
Neoplasms, Radiation-Induced - pathology
Papilloma - genetics
Pigmentary diseases of the skin
Precancerous Conditions - genetics
Precancerous Conditions - pathology
Radiation Dosage
Skin - radiation effects
Skin Neoplasms - genetics
Skin Neoplasms - pathology
Tumors of the skin and soft tissue. Premalignant lesions
Xeroderma Pigmentosum - genetics
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Summary:Although xeroderma pigmentosum (XP) patients are rare, carriers of XP genes (heterozygotes) are much more common. Whether such carriers have an increased skin cancer risk is unknown. Recently developed mouse models for XP have opened up the possibility of determining the skin cancer risk of heterozygotes relative to wild types. Therefore, the XPA knockout trait has been crossed into hairless mice, and squamous cell carcinomas of the skin have been induced by low daily UVB exposures for 500 days in all three genotypes (-/-, +/-, and +/+). The carcinogenic response of the heterozygotes did not significantly differ from that of their wild-type littermates. Tumors in the XPA -/- animals appeared with a latency time that was decreased by a factor of 4.2. From this, we estimate that a functional XPA gene provides a "protection factor" of 60 (95% confidence interval, 15-250) against UV carcinogenesis, which is greater protection than that against acute UV effects, such as erythema and edema (protection factor between 7 and 16). Deficient nucleotide excision repair appears to have a more dramatic impact on skin cancer susceptibility than on sensitivity to acute UV effects.
ISSN:0008-5472
1538-7445