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The present study was designed to further investigate the role of reactive oxygen species in the mechanism of action of anthrone tumor promoters. To accomplish this, the effects of several antioxidants on the induction of epidermal ornithine decarboxylase (ODC) activity, epidermal hyperplasia, skin
The skin tumor-promoting ability of 1,8-dihydroxy-3-methyl-9-anthrone (chrysarobin) was compared with that of 12-O-tetradecanoylphorbol-13-acetate (TPA) and 1,8-dihydroxy-9-anthrone (anthralin) in SENCAR mice. Although dose-response comparisons indicated that chrysarobin was several orders of
The present study examined the effect of several prototypic inhibitors of phorbol ester skin tumor promotion on skin tumor promotion by chrysarobin, an anthrone tumor promoter. Retinoic acid (RA) inhibited skin tumor promotion by chrysarobin; however, the degree of inhibition was dependent on the
The characteristics of the skin tumor promotion response with anthrone derivatives has been further examined in SENCAR mice. Chrysarobin (1,8-dihydroxy-3-methyl-9-anthrone) was an effective skin tumor promoter when applied twice weekly with dose-dependent increases in both papillomas and squamous
Histologic changes induced in SENCAR skin following a single treatment with chrysarobin (1,8-dihydroxy-3-methyl-9-anthrone) exhibited differences in time course from that observed with 12-O-tetradecanoylphorbol-13-acetate (TPA). Although not significantly different, maximum elevations in epidermal
The present study was designed to compare the skin tumor promoting and epidermal ornithine decarboxylase (ODC) inducing activities of various structural analogs of anthralin (1,8-dihydroxy-9-anthrone) and chrysarobin (1,8-dihydroxy-3-methyl-9-anthrone). Groups of 30 SENCAR mice each were initiated
Two genetic models that could explain all of the current data are depicted in Figure 4, although it should be stressed that proof of any model will require additional genetic analyses. The first model (Model A) indicates that one or more loci controlling responsiveness to TPA are also responsible
The present study has compared different mouse stocks and strains with known sensitivity to phorbol ester skin tumor promotion for their sensitivities to skin tumor promotion by a prototypic organic peroxide (benzoyl peroxide, BzPo) and anthrone (chrysarobin, Chr) tumor promoter. Following
Genetic susceptibility to two-stage skin carcinogenesis is known to vary significantly among different stocks and strains of mice. In an effort to identify specific protein changes or altered signaling pathways associated with skin tumor promotion susceptibility, a proteomic approach was used to
A single topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA) to mouse skin decreased 125I-labeled epidermal growth factor (EGF) binding in epidermal membrane preparations within 1 h while 1,8-dihydroxy-3-methyl-9-anthrone (chrysarobin) gradually reduced binding with maximum inhibition
A single topical application of chrysarobin (220 nmol) to SENCAR mouse skin produced alterations in epidermal polyamine levels distinctly different from that following a single topical treatment with 3.4 nmol of 12-O-tetradecanoylphorbol-13-acetate (TPA). Putrescine and spermidine levels were
Insulin-like growth factor-1 (IGF-1) and its receptor are believed to play an important role in mitogenesis and neoplastic transformation. The purpose of this study was to further examine the role of IGF-1 during tumor promotion in mouse skin. HK1.IGF1 transgenic mice, which overexpress IGF-1 in
The present study was designed to further investigate the role of the epidermal growth factor receptor (EGFr) in mouse skin tumor promotion by evaluating the status of the EGFr in tumor promoter-treated mouse epidermis and in mouse skin tumors. Female SENCAR mice received three topical treatments of
The current study was designed to explore the role of signal transducer and activator of transcription 1 (Stat1) during tumor promotion using the mouse skin multistage carcinogenesis model. Topical treatment with both 12-O-tetradecanoylphorbol-13-acetate (TPA) and 3-methyl-1,8-dihydroxy-9-anthrone
Akt is a serine/threonine kinase involved in a variety of cellular responses, including cell proliferation and cell survival. Recent studies from our laboratory suggest that Akt signaling may play an important role in skin tumor promotion. To explore this premise, we examined epidermal Akt