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The study demonstrated that K6/ODC transgenic mice, which overexpress ornithine decarboxylase (ODC) in hair follicle keratinocytes, served as a sensitive model for identifying genotoxic carcinogens. The model showed 100% concordance with traditional 2-year rodent bioassays when tested with 10 known carcinogens or noncarcinogens. Notably, it successfully identified human carcinogens and demonstrated tumor development at low doses of 7,12-dimethylbenz(a)anthracene (DMBA). This model offered advantages such as shorter test times and fewer animals, making it a promising tool for carcinogen identification and chemical risk assessment.

The study tested whether suppressing ornithine decarboxylase (ODC) activity could block skin tumor promotion in mice with activated MEK mutations. By crossing these mice with those overexpressing antizyme (AZ), which degrades ODC, researchers found that AZ expression significantly delayed tumor development and reduced tumor numbers. This effect was most pronounced in MEK/K6-AZ mice, which had fewer than one tumor per mouse after 8 weeks, compared to over 13 tumors in MEK-only mice. The study suggested that AZ primarily inhibited putrescine accumulation, slowing cell growth by increasing G2/M transit time, without inducing apoptosis.

The study investigated the effects of TPA-stimulated polyamine biosynthesis on metastatic squamous cell carcinoma (mSCC) development in protein kinase C epsilon (PKC epsilon) transgenic mice. It was found that TPA treatment significantly increased epidermal ornithine decarboxylase (ODC) activity and putrescine levels in these mice compared to wild-type littermates. The development of mSCC was completely prevented by administering alpha-difluoromethylornithine (DFMO), an ODC inhibitor, in the drinking water during TPA promotion. However, this treatment resulted in marked hair loss and a decrease in intact hair follicles in the transgenic mice. The findings suggested a link between TPA-induced ODC activity, putrescine accumulation, hair follicle maintenance, and mSCC development, with the observed hair loss being a novel side effect not previously reported in other cancer prevention models.

The study explored the impact of ornithine decarboxylase (ODC) overexpression in hair follicle keratinocytes on stem cell behavior and tumorigenesis, particularly its interaction with Notch signaling. Using two mouse models, K6-ODC/SKH-1 and K14-ODC/SKH-1, it was found that ODC overexpression in K6-ODC/SKH-1 mice led to a significant increase in tumor development and invasiveness, with 15±2.5 tumors per mouse compared to 6.8±1.5 in K14-ODC/SKH-1 mice. This was linked to an expansion of the stem cell compartment and a down-regulation of Notch signaling, suggesting that ODC may enhance skin carcinogenesis by promoting stem-like cancer-initiating cells and contributing to invasive squamous cell carcinomas.

The study investigated the effect of dimethylarsinic acid (DMA) on skin carcinogenesis in K6/ODC transgenic mice, which are more sensitive to carcinogens due to the overexpression of ornithine decarboxylase in hair follicle keratinocytes. Female C57BL/6J K6/ODC transgenic mice were treated with DMA after initiation with 7,12-dimethylbenz[α]anthracene (DMBA). The results showed that DMA significantly accelerated the induction of skin tumors, similar to the known tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), indicating that DMA had a promoting effect on skin tumorigenesis in these transgenic mice.

The study investigated the role of polyamines in hair follicle function and fiber composition in sheep. It found that inhibiting ornithine decarboxylase with alpha difluoromethylornithine altered fiber characteristics but did not inhibit wool follicle growth in culture. Conversely, inhibiting S-adenosylmethionine decarboxylase with methylglyoxal (bis)guanylhydrazone completely inhibited fiber growth, which could be reversed by adding spermidine, but not spermine. The study concluded that polyamines, particularly spermidine, were crucial for hair growth, as evidenced by the ability of spermidine to partially counteract growth depression in methionine-deficient conditions.

The study revealed a negative regulatory loop between the Hairless (HR) protein and the polyamine putrescine in the epidermis, impacting hair follicle cycling and epidermal homeostasis. HR regulated ornithine decarboxylase (ODC) expression through MYC superfamily proteins, while elevated putrescine levels decreased HR expression. This mutual regulation was linked to hair loss phenotypes in mouse models with altered HR or polyamine enzyme expression. The research suggested that putrescine influenced gene expression through various pathways, including epigenetic mechanisms, affecting a small number of genes in keratinocytes. These findings highlighted the complex regulatory mechanisms involving HR and polyamines, with implications for hair cycling and potentially carcinogenesis.

The study investigated a cream with 4% capryloyl glycine and 1% soy isoflavonoids for treating hypertrichosis on the forearms of 12 Caucasian female patients. The cream significantly reduced ornithine decarboxylase 1 (ODC1) activity by 35.1%. After four months, 91.7% of patients using the cream showed improvement, with 58.3% experiencing good efficacy and 41.7% moderate efficacy, while the placebo group showed no improvement. The cream was well-tolerated, with no adverse events and good cosmetic acceptability. The study concluded that the cream effectively reduced hair growth in the tested population, but recommended further trials with more participants to confirm these findings.

The study used transgenic mice to explore the role of MEK and Antizyme (AZ) in skin tumorigenesis and keratinocyte differentiation. Mice overexpressing MEK showed increased epidermal hyperplasia, tumor development, and expansion of epidermal stem cells, with decreased keratinocyte differentiation. However, co-expression of AZ reduced tumor development and normalized the number of transient amplifying (TA) cells and stem cells, counteracting the effects of MEK. AZ also restored normal levels of differentiation markers in keratinocytes, suggesting that AZ can mitigate MEK-induced suppression of differentiation. The findings indicated that ornithine decarboxylase (ODC) and polyamines played crucial roles in regulating epidermal stem cell expansion and keratinocyte progenitor cell differentiation.

In this study, transgenic mice overexpressing spermidine/spermine N1-acetyltransferase (SSAT) experienced permanent hair loss by 3 weeks of age due to the overaccumulation of putrescine, which disrupted normal hair follicle development. Although these mice completed the first hair cycle normally, they showed early signs of hair follicle degeneration and failed to enter the second anagen phase, resulting in the replacement of hair follicles with dermal cysts and epidermal utriculi. Elevated putrescine levels were linked to continuous epithelial cell proliferation, potentially causing follicular cysts and epidermal thickening. Hybrid mice with both ornithine decarboxylase (ODC) and SSAT overexpression exhibited even higher putrescine levels and more severe skin issues. Interestingly, SSAT mice were more resistant to papilloma development in a skin carcinogenesis model, possibly due to the inability of tumor-promoting agents to induce ODC or increase skin spermidine levels. The study highlighted the crucial role of putrescine in hair follicle development and its excessive accumulation's contribution to the hairless phenotype.

The study investigated hair regrowth in C3H mice of varying ages by examining enzyme activities in different skin areas after shaving. It was found that hair regrowth was irregular and delayed as the mice aged, with older mice showing more significant delays. Biochemical analysis of 18 mice revealed that enzyme activities, specifically ornithine decarboxylase (ODC), transglutaminase (TGase), and alkaline phosphatase (Al-P), were significantly higher in areas where hair was regrowing compared to non-growing areas. This suggested that these enzymes played a role in hair regrowth, with increased activity in follicle-rich regions.

The study investigated the effects of cigarette smoke condensates (CSCs) on mouse skin, focusing on hyperplasia and inflammation as short-term biomarkers of tumor promotion. Using a truncated initiation-promotion protocol, the research assessed epidermal thickness, proliferative index, and ornithine decarboxylase (ODC) expression after CSC application. Results showed that CSCs increased these markers, with partial reversibility in interfollicular areas but sustained elevation in perifollicular regions. The study highlighted perifollicular ODC expression as a promising indicator for evaluating CSCs due to its rapid induction, low threshold, and potential to reflect irreversible changes, aligning with the notion that ODC expression is crucial for tumor promotion and that tumors primarily originate in the perifollicular epidermis.

The study investigated the response of mitogen-regulated protein/proliferin (mrp/plf) mRNA to tumor promoters in murine skin. Researchers applied tumor promoters, such as 12-O-tetradecanoylphorbol-13-acetate (TPA) and benzoyl peroxide (BPO), to the skin of SENCAR mice and analyzed RNA samples from treated areas. They found that mrp/plf-mRNA was not detected in Northern blot hybridizations, but significant increases in mRNAs for genes like ornithine decarboxylase and junB were observed in response to TPA. Reverse transcriptase-polymerase chain reactions revealed fully-processed MRP/plf-mRNA in most TPA-treated and some BPO-treated animals, with predominant expression of plf1 and mrp3. The study concluded that mrp/plf-mRNA was differentially expressed in response to tumor promoters and could serve as a biomarker for tumor-promoting effects in chemical carcinogenesis.