Oxidative dna damage and modulation of p53 tumor suppressor gene as possible mechanisms of chromium carcinogenicity( part i)

Introduction: Chromium, like many transition metal elements, is essential to life at low concentrations yet toxic to many systems at higher concentrations. Toxic effects of chromium can be classified into sensitizing, caustic and carcinogenic effects. Chromium is one of the best known sensitizing agents; it causes allergic dermatitis, allergic rhinitis and occupational asthma. There is sufficient evidence of the carcinogenicity of various chromium compounds in humans encountered via inhalation in industrial applications. Aim of work: to assess the carcinogenic potential of chromium exposure in tannery workers and study the possible mechanisms using 8-hydroxydeoxyguanosine (8-OHdG) which is one of the major oxidative adducts formed by radical induced damage to DNA, TAC (total anti-oxidant capacity) as a biomarker of cellular oxidative stress and p53 as apoptotic regulatory protein. Materials and methods: This work was carried out in twelve small-to medium-sized tanneries, in Misr Al Kadema district in Cairo. The study comprised of two groups, an exposed group (45 male workers) and a matched control group (30 male workers). All workers were subjected to a detailed history including present, past, family and occupational history. Clinical examination was performed with special emphasis on chest and skin examination. Laboratory investigations were performed in the form of kidney function test (blood urea and serum creatinine), blood level of TAC, P53 and chromium. Also, urinary 8-OHdG was done. Results: we found a significant increase in chromium, TAC, p53 and urinary 8-OHG in the exposed group compared to their referent control. Significant positive correlation was detected between P53 with blood level of TAC. Conclusion: Our results revealed that tannery workers have increased level of blood chromium, and this increase is associated with oxidative damage especially oxidative DNA damage reflected by elevated TAC serum level and  urinary 8-OHG. Also, up-regulation or activation of serum p53 in tannery workers which was positively correlated with chromium (non-significant) and significantly positively correlated with TAC reinforce the possible relation between oxidative stress induced by chromium exposure and carcinogenesis