We examined the clonal evolution of skin malignant lesions by repeated topical applications of @entity5954 (20-MC) to the skin, which induces @entity5072 , @entity75 and @entity189 in @entity19 . The lesions were examined histologically and immunohistochemically with anti-single-stranded DNA after acid hydrolysis (DNA-instability test), @entity899 , @entity1611 , @entity70429 , @entity4698 and AgNORs parameters analyses. Multiple clones with increased DNA instability comparable to that of @entity189 were noted in early-stage (2-6 weeks) @entity5072 , and their number increased in middle (7-11 weeks), and late-stages (12-25 weeks) of @entity5072 , indicating that they belong to the @entity5 category. All @entity189 showed a positive DNA-instability test. Positive immunostaining for various biomarkers and AgNORs parameters appeared in clones with a positive DNA-instability test in early-or middle-stage @entity5072 , and markedly increased in late-stage @entity5072 , @entity189 . The percentage of @entity4698 -positive vascular endothelial cells was significantly higher in @entity1611 -positive lesions with a positive DNA-instability test and became higher toward the late-stage of progression. Cut-woundings were made to @entity189 lesions, and the regeneration activity of vascular endothelial cells was determined by using flash labeling with tritiated @entity1014 (3H-TdR). In small @entity75 , vascular endothelial cells showed regenerative response, but the response was weak in large lesions. No such response was noted in invasive @entity189 ; rather, cut-wounding induced collapse of blood vessels, which in turn induced @entity11659 of @entity5 cells. These responses can be interpreted to reflect exhausted vascular growth activity due to excessive stimulation by @entity1611 -overexpression, which was persistently seen from @entity5072 to @entity189 .

Clonal evolution and progression of @entity5954 -induced squamous cell carcinoma of XXXX epidermis as revealed by DNA instability and other @entity5 markers.

@entity75 :: ('MESH:D001927', 'Disease') :: ['papillomatous lesion', 'papillomatous lesions'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity5072 :: ('MESH:D000796', 'Disease') :: ['hyperplastic epidermis'] @entity899 :: ('22060(Tax:10090)', 'Gene') :: ['p53'] @entity70429 :: ('13347(Tax:10090)', 'Gene') :: ['DFF45'] @entity189 :: ('MESH:D002277', 'Disease') :: ['carcinomas', 'papillomatous lesions and invasive carcinomas', 'papillomatous and invasive carcinoma', 'invasive carcinoma'] @entity5 :: ('MESH:D009369', 'Disease') :: ['cancer', 'malignancy'] @entity4698 :: ('18538(Tax:10090)', 'Gene') :: ['PCNA'] @entity1014 :: ('MESH:D013936', 'Chemical') :: ['thymidine'] @entity1611 :: ('22339(Tax:10090)', 'Gene') :: ['VEGF'] @entity5954 :: ('MESH:D008748', 'Chemical') :: ['20-methylcholanthrene'] @entity11659 :: ('MESH:D047508', 'Disease') :: ['massive coagulative necrosis']
@entity19 :: (10090,Species) :: ['mouse']
