Recent evidence suggests that an initial barrier to the emergence of tumours is a DNA damage response that evokes a counter-response which arrests the growth of, or eliminates, damaged cells. Early precursor lesions express markers of an activated DNA damage response in several types of tumour, with a diminishing response in more advanced cancers. An important marker of DNA damage is ATM which becomes phosphorylated (pATM) upon activation. We have investigated pATM expression patterns in cultured keratinocytes, skin explants and a spectrum of pre-malignant to malignant keratinocyte skin lesions by immunohistochemistry. We found that pATM was mainly localised to the Golgi apparatus, which contrasts with its nuclear localisation in other tissues. Upon UV irradiation there is transient formation of pATM in nuclear foci, consistent with recruitment to the sites of DNA damage. By immunohistochemistry we show pATM expression in precancerous keratinocyte lesions is greater and predominantly nuclear when compared to the invasive lesions where pATM is weaker and predominantly cytoplasmic. Our results are consistent with the hypothesis that the DNA damage response acts as a barrier to cutaneous tumour formation, but also suggests that ATM expression in skin is different compared to other tissues. This may be a consequence of the constant exposure of skin to UVR, and has implications for skin carcinogenesis.
Three hundred sixty-nine male blood donors from Medina Munawara were studied for hepatitis B virus (HBV) markers. Serologic evidence of exposure to HBV was noted in 48%. A majority of these individuals showed the presence of antibodies, and only 7.6% were documented as HBsAg carriers. The infection was usually caused by HBV subtype ay. A strong positive correlation existed between infection rate, age, and poor socioeconomic conditions. We presume that improvement in the socioeconomic conditions and timely vaccination may help in reducing the infection rate. The discovery of hepatitis B surface antigen (HBsAg) by Blumberg et al 1 led to the recognition that blood or blood products of a healthy donor could be infectious. In order to avoid post-transfusion hepatitis, sensitive methods were developed to test the blood and blood products for hepatitis B virus (HBV) markers, and the prevalence of these markers was studied in various parts of the world. In Saudi Arabia several studies have been conducted to assess the prevalence of HBsAg among the healthy population. The results of these studies show that the rate varies from 2% to 20% depending on the detection method used and the population studied. [3][4][5] HBsAg is present in about 8% to 12% of the Saudi male blood donors in the Eastern Province and Riyadh, 6-8 while 20% to 26% of Saudi males in Gizan and Khaiber areas may be termed as carriers. 4,5 As variation exists in the rates of HBV infection in different parts of the country, the present study was undertaken to determine the frequency of HBV markers in the blood donors in Medina Munawara and to find the predominant HBsAg subtype (ad or ay) among the carriers.It has been suggested that in the absence of serologic markers for HBV, unexplained elevation of alanine aminotransferase (ALT) could be due to the presence of non-A, non-B virus.9 Therefore, serum ALT levels were also determined in this study to assess the frequency of the non-A, non-B carrier state. Materials and MethodsDuring the period of October 1986 to March 1987 blood specimens were collected at the Central Blood Bank, Medina Munawara, on a random basis from 369 healthy blood donors, who were required by the Ministry of Interior to donate blood before they were issued a Saudi driver's license. Each donor completed a form to provide information pertaining to age, marital status, education, and nationality. Among the donors, 234 were Saudi nationals, while the non-Saudi group comprised 20 different nationalities. An aliquot of specimen was allowed to clot; serum was separated by centrifugation, and pending analysis, sera were stored frozen at -20°C. Estimation of ALT on these samples was carried out as early as possible, mostly within 1 week of collection.
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