Loss of tyrosinase activity confers increased skin tumor susceptibility in mice

Saran, Anna; Spinola, Monica; Pazzaglia, Simonetta; Peissel, Bernard; Tiveron, Cecilia; Tatangelo, Laura; Mancuso, Mariateresa; Covelli, Vincenzo; Giovannelli, Lisa; Pitozzi, Vanessa; Pignatiello, Carmen; Milani, Silvano; Dolara, Piero; Dragani, Tommaso A.

doi:10.1038/sj.onc.1207565

Cited by 24 publications

(13 citation statements)

References 25 publications

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“…Tomaso Dragani's group also mapped Skts1 using Car-R and Car-S outbred. crosses [14], which were generated by balanced intercross of inbred strains, and reported loss of tyrosinase activity conferred increased skin tumor susceptibility [15]. Skts13 was identified as the Aurka gene [16], and Skts14 was identified as Tgfb1 [11].…”

Section: Introductionmentioning

confidence: 99%

New chemically induced skin tumour susceptibility loci identified in a mouse backcross between FVB and dominant resistant PWK

et al. 2007

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Background: A variety of skin cancer susceptibility among mouse strains has allowed identification of genes responsible for skin cancer development. Fifteen Skts loci for skin tumour susceptibility have been mapped so far by using the two-stage skin carcinogenesis model [induced by 7.12-dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)]. A few responsible genes have been identified using wild-derived dominant resistant Mus spretus mice, and one has been confirmed as a low penetrance cancer susceptibility gene in a variety of human cancers.

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Section: Introductionmentioning

confidence: 99%

New chemically induced skin tumour susceptibility loci identified in a mouse backcross between FVB and dominant resistant PWK

et al. 2007

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“…42 In this regard, inhibition of cutaneous tyrosinase by AO and isolated sanguinarine makes the DNA molecules vulnerable to oxidative attack as observed in the results of Comet assay in dropsy patients of the present study. Further, decrease of dermal non-enzymatic (GSH) and enzymatic antioxidants such as catalase, SOD, GSH reductase and GSH peroxidase by AO and sanguinarine may lead to enhanced accumulation of lipid peroxides that ultimately cause DNA damage leading to carcinogenesis.…”

Section: Discussionmentioning

confidence: 72%

Correlation of DNA damage in epidemic dropsy patients to carcinogenic potential of argemone oil and isolated sanguinarine alkaloid in mice

Das

Ansari

Dhawan

et al. 2005

Intl Journal of Cancer

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In recent times, a higher incidence of gall bladder carcinoma in the Indo‐Gangetic basin has been linked with the consumption of contaminated mustard oil. Consumption of mustard oil contaminated with argemone oil (AO) is well known to cause clinical manifestation referred to as “epidemic dropsy.” Because sanguinarine, an active alkaloid of AO, has been shown to intercalate DNA, a possible correlation of DNA damage in epidemic dropsy patients to tumorigenic potential of AO and isolated sanguinarine alkaloid in mice was investigated in the present study. Single topical application of AO (0.15–0.3 ml) or isolated sanguinarine (4.5–18 μmol) followed by twice‐weekly application of tetradecanoylphorbolmyristate acetate (TPA) for 25 weeks resulted in formation of tumors. Histopathologically these tumors were of squamous cell carcinoma type and similar to those found in the positive control group using dimethylbenzanthracene (DMBA)/TPA. The activities of cutaneous γ‐glutamyl transpeptidase (GGT) and glutathione‐S‐transferase P (GST‐P), marker enzymes of tumorigenesis, were found to exhibit higher expression in AO or isolated sanguinarine/TPA treated groups when compared to control. The higher expression of p53 and p21/WAF1 in skin after single topical application of AO or isolated sanguinarine further confirms the tumorigenic response. Single topical application of AO or isolated sanguinarine alkaloid to mice showed significant DNA damage in terms of Olive tail moment (89–129%), tail length (54%) and tail DNA (153–205%) using Comet assay in skin cells. Further, the extent of DNA damage in blood cells of epidemic dropsy patients in alkaline Comet assay was found to be significantly higher as compared to normal population, indicating the genotoxic response of AO exposure. Although the genotoxic lesions may be repaired to some extent on withdrawal of consumption of AO contaminated mustard oil and the residual genotoxic effects caused by AO may not be expressed as signs of carcinogenesis. Environmental factors or hormonal changes during aging process may lead to stimulate/promote the genetically altered latent cells to form neoplastic lesions and can act as one of the etiological factors responsible for higher incidence of gall bladder carcinoma in the population of Indo‐Gangetic basin. © 2005 Wiley‐Liss, Inc.

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“…Topical application of TOCO and NAC to AO/TPA-and SANG/TPAinduced animals enhances the decreased activity of tyrosinase. Since loss of tyrosinase activity has been related to skin tumor susceptibility in mice due to the deficiency of melanin pigment production, thereby modulating oxidative DNA damage (44). Thus the present results of TOCO and NAC may indicate the protective role for DNA molecule from oxidative attack caused by AO and SANG, which may be one of the possible mechanism of anticarcinogenic activity.…”

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confidence: 77%

Protective Effect of Topical Application of α-Tocopherol and/or N-Acetyl Cysteine on Argemone Oil/Alkaloid-Induced Skin Tumorigenesis in Mice

Pal

Alam

Singhal

et al. 2013

Nutrition and Cancer

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Since bioantioxidants in plasma of Epidemic Dropsy patients [a condition caused by consumption of adulterated mustard oil with argemone oil (AO)] were found to be significantly decreased, the beneficial effect of N-acetyl cysteine (NAC) and α-tocopherol (TOCO) against AO- or sanguinarine (SANG)-induced tumorigenicity was undertaken in mice. Topical application of TOCO and NAC either alone or in combination showed significant protection against AO/TPA- and SANG/TPA-induced skin tumorigenicity. Histopathological findings suggest that papillomatous growth in AO/TPA- and SANG/TPA-treated animals were substantially protected following topical application of TOCO or NAC. Further, treatment of TOCO and NAC either alone or in combination to AO/TPA- or SANG/TPA-induced mice significantly decreased lipid peroxidation, along with significant revival in glutathione (GSH) content and activities of tyrosinase, histidase, catalase, SOD, GSH peroxidase, and GSH reductase in skin. In vitro studies showed that TOCO and/or NAC significantly decreased the AO and SANG induced cell proliferation and activation of ERK, p38, JNK MAPKs and NF-κB signaling in HaCaT cells. In summary, TOCO and NAC may be useful in preventing the tumorigenic response of AO and SANG probably by acting as scavenger of free radicals and inhibiting MAPKs and NF-κB signaling.

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Loss of tyrosinase activity confers increased skin tumor susceptibility in mice

Cited by 24 publications

References 25 publications

New chemically induced skin tumour susceptibility loci identified in a mouse backcross between FVB and dominant resistant PWK

New chemically induced skin tumour susceptibility loci identified in a mouse backcross between FVB and dominant resistant PWK

Correlation of DNA damage in epidemic dropsy patients to carcinogenic potential of argemone oil and isolated sanguinarine alkaloid in mice

Protective Effect of Topical Application of α-Tocopherol and/or N-Acetyl Cysteine on Argemone Oil/Alkaloid-Induced Skin Tumorigenesis in Mice

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