Induction of nevi and skin tumors in Ink4a/Arf Xpa knockout mice by neonatal, intermittent, or chronic UVB exposures.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
AuthorsSchanke, Arne van
Venrooij, Gemma M C A L van
Jongsma, Marjan J
Banus, H Alexander
Mullenders, Leon H F
Kranen, Henk J van
Gruijl, Frank R de
MetadataShow full item record
TitleInduction of nevi and skin tumors in Ink4a/Arf Xpa knockout mice by neonatal, intermittent, or chronic UVB exposures.
PubliekssamenvattingNevi and melanomas correlate to childhood and intermittent solar UV exposure, xeroderma pigmentosum patients run increased risk, and p16(Ink4a) expression is often lost in malignant progression. To ascertain the effect of these risk factors, pigmented hairless Ink4a/Arf-, Xpa- knockout mice were subjected to various combinations of neonatal [7,12-dimethylbenz(a)anthracene (DMBA) or UVB exposure] and adult treatments (12-O-tetradecanoylphorbol-13-acetate or subacute daily UVB exposure or intermittent overexposure). Nevi occurred earliest, grew largest, and were most numerous in mice exposed to DMBA followed by intermittent UVB overexposure [effect of six minimal edemal doses (MED), 1 x /2 weeks > 4 MED 1 x /wk]. Neonatal UV exposure enhanced nevus induction but lost its effect after 200 days. The Xpa(-/-) mice proved exquisitely sensitive to UV-driven nevus induction, indicating the involvement of pyrimidine dimer DNA lesions, but Xpa(+/+) mice developed many more nevi (>40 per mouse) at high UV dosages not tolerated by Xpa(-/-) mice. Ink4a/Arf(-/-) mice developed most skin tumors faster, but surprisingly developed nevi slower than their heterozygous counterparts especially after neonatal UV exposure. Despite raising >1,600 nevi, only six melanomas arose in our experiments with Ink4a/Arf knockout mice (five of which in Xpa(+/+) mice at high UV dosages). In contrast to human nevi, these nevi lacked hotspot mutations in Braf or Ras genes, possibly explaining the lack of malignant progression in the Ink4a/Arf(-/-) mice. Hence, although our experiments did not effectively emulate human melanoma, they provided clear evidence that intermittent UV overexposure strongly stimulates and the Ink4a/Arf(-/-) genotype may actually impair nevus development.
- INK4a-ARF mutations in skin carcinomas from UV irradiated hairless mice.
- Authors: Soufir N, Queille S, Mollier K, Roux E, Sarasin A, de Gruijl FR, Fourtanier AM, Daya-Grosjean L, Basset-Seguin N
- Issue date: 2004 Apr
- Ink4a/arf deficiency promotes ultraviolet radiation-induced melanomagenesis.
- Authors: Recio JA, Noonan FP, Takayama H, Anver MR, Duray P, Rush WL, Lindner G, De Fabo EC, DePinho RA, Merlino G
- Issue date: 2002 Nov 15
- Early p53-positive foci as indicators of tumor risk in ultraviolet-exposed hairless mice: kinetics of induction, effects of DNA repair deficiency, and p53 heterozygosity.
- Authors: Rebel H, Mosnier LO, Berg RJ, Westerman-de Vries A, van Steeg H, van Kranen HJ, de Gruijl FR
- Issue date: 2001 Feb 1
- Role of ultraviolet radiation in the induction of melanocytic tumors in hairless mice following 7,12-dimethylbenz(a)anthracene application and ultraviolet irradiation.
- Authors: Husain Z, Pathak MA, Flotte T, Wick MM
- Issue date: 1991 Sep 15
- Association between INK4a-ARF and p53 mutations in skin carcinomas of xeroderma pigmentosum patients.
- Authors: Soufir N, Daya-Grosjean L, de La Salmonière P, Moles JP, Dubertret L, Sarasin A, Basset-Seguin N
- Issue date: 2000 Nov 15