Isoconazole and Clemizole Hydrochloride Partially Reverse the Xeroderma Pigmentosum C Phenotype
نویسندگان
چکیده
Xeroderma Pigmentosum protein C (XPC) is involved in recognition and repair of bulky DNA damage such as lesions induced by Ultra Violet (UV) radiation. XPC-mutated cells are, therefore, photosensitive accumulate UVB-induced pyrimidine dimers leading to increased cancer incidence. Here, we performed a high-throughput screen identify chemicals capable normalizing the XP-C phenotype (hyper-photosensitivity accumulation photoproducts). Fibroblasts from patients were treated with library approved chemical drugs. Out 1280 tested chemicals, 16 showed ?25% photo-resistance RZscore above 2.6 two drugs able favor 6-4 pyrimidone photoproducts (6-4PP). Among these compounds, Isoconazole could partially inhibit apoptosis irradiated especially when post-treated directly after UV irradiation while Clemizole Hydrochloride-mediated increase viability was dependent on both pre post treatment. No synergistic effect recorded following combined drug treatment compounds exerted no proliferative capacity exposure. Amelioration pave way towards understanding accelerated skin initiation patients. Further examination required decipher molecular mechanisms targeted chemicals.
منابع مشابه
XPC ( xeroderma pigmentosum , complementation group C )
Protein Description 939 amino acids. Expression Ubiquitous. Localisation Nuclear. Function Involved in the early recognition of DNA damage present in chromatine. Two proteins have been identified and implicated in (one of) the first steps of NER, i.e. the recognition of lesions in the DNA: the XPA gene product and the XPC gene product in complex with HR23B. This XPC-HR23B complex has been impli...
متن کاملXeroderma pigmentosum.
OBJECTIVE To describe the features of Xeroderma pigmentosum observed in the stage 3 of the disease. STUDY DESIGN Case series. PLACE AND DURATION OF STUDY Mayo Hospital Lahore, from December 2001 to September 2008. METHODOLOGY All patients diagnosed with Xeroderma pigmentosum stage 3 in the outpatient department of the study centre, were included. The age at first presentation, tumour site...
متن کاملXeroderma pigmentosum.
Seven cases of XP seen during a relatively short period of time, possibly indicate a high frequency of this gene in this part of the country. The gene frequency in the general population has been reported to be 1 in 200 million and the frequency of the disorder, 4 in 1 million(3). Countries like Libya, Egypt, Israel and Japan, with a high degree of consanguinity, have a high incidence of this d...
متن کاملXeroderma pigmentosum
Xeroderma pigmentosum (XP) is defined by extreme sensitivity to sunlight, resulting in sunburn, pigment changes in the skin and a greatly elevated incidence of skin cancers. It is a rare autosomal recessive disorder and has been found in all continents and racial groups. Estimated incidences vary from 1 in 20, 000 in Japan to 1 in 250, 000 in the USA, and approximately 2.3 per million live birt...
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ژورنال
عنوان ژورنال: International Journal of Molecular Sciences
سال: 2021
ISSN: ['1661-6596', '1422-0067']
DOI: https://doi.org/10.3390/ijms22158156