Document Detail


Induction of nevi and skin tumors in Ink4a/Arf Xpa knockout mice by neonatal, intermittent, or chronic UVB exposures.
MedLine Citation:
PMID:  16510579     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Nevi 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.
Authors:
Arne van Schanke; Gemma M C A L van Venrooij; Marjan J Jongsma; H Alexander Banus; Leon H F Mullenders; Henk J van Kranen; Frank R de Gruijl
Related Documents :
20044279 - Treatment with telmisartan attenuates graft arteriosclerosis in murine cardiac allografts.
22558139 - Cathepsin s deficiency results in abnormal accumulation of autophagosomes in macrophage...
16982899 - Identification of susceptibility loci for skin disease in a murine psoriasis model.
14510979 - Proinflammatory cytokines upregulate expression of calprotectin (l1 protein, mrp-8/mrp-...
10233769 - Inhibition of solar simulator-induced p53 mutations and protection against skin cancer ...
16407659 - Skin-derived micro-organs induce angiogenesis in rabbits.
23169919 - The novel proteasome inhibitor bsc2118 protects against cerebral ischaemia through hif1...
2285599 - Cytokines and the hypothalamic-pituitary-adrenal axis.
6862149 - Antitumor activity of 2-keto-3-deoxyoctonate-free lipopolysaccharide of vibrio anguilla...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cancer research     Volume:  66     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  2006 Mar 
Date Detail:
Created Date:  2006-03-02     Completed Date:  2006-04-18     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2608-15     Citation Subset:  IM    
Affiliation:
Dermatology Department, University Medical Centre Utrecht, Utrecht, the Netherlands.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
9,10-Dimethyl-1,2-benzanthracene
Animals
Carcinoma, Squamous Cell / etiology,  genetics
Cocarcinogenesis*
Cyclin-Dependent Kinase Inhibitor p16 / deficiency,  genetics*
Melanoma, Experimental / etiology,  genetics
Mice
Mice, Knockout
Neoplasms, Radiation-Induced / chemically induced,  etiology*,  genetics
Nevus / etiology*,  genetics
Sarcoma / etiology,  genetics
Skin Neoplasms / chemically induced,  etiology*,  genetics
Tumor Suppressor Protein p14ARF / deficiency,  genetics*
Ultraviolet Rays
Xeroderma Pigmentosum Group A Protein / genetics*
Chemical
Reg. No./Substance:
0/Cyclin-Dependent Kinase Inhibitor p16; 0/Tumor Suppressor Protein p14ARF; 0/Xeroderma Pigmentosum Group A Protein; 0/Xpa protein, mouse; 57-97-6/9,10-Dimethyl-1,2-benzanthracene

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Normoxic stabilization of hypoxia-inducible factor-1alpha by modulation of the labile iron pool in d...
Next Document:  Activation of human long interspersed nuclear element 1 retrotransposition by benzo(a)pyrene, an ubi...