Mutation rate is a key feature of somatic cells which has been difficult to measure in humans. Mutation rate, in association with the number of cell divisions, is likely correlated with the risk of cancer. However, the correlation between mutation rate and cancer has been explored only for rare diseases, like ataxia talangectasia and Fanconi anemia, in which mutation rate is considerably elevated. Oxidation damage is also a key cell pathological event, involved in senescence, inflammation and cancer and inducing loss of function of proteins, lipids, DNA and RNA. In DNA, oxidation damage induces the formation of about twenty different oxidation products, the most important of which is 8-oxodeoxyguanine, which induces code errors and mutations. However, oxidised bases are effectively repaired to conserve DNA integrity, and the presence of a reduced activity of one of the enzymes removing oxidized bases (8-oxoguanosine glycosylases 1, OGG1) is associated with a higher risk of neoplasms, like head and neck cancer. Oxidation damage is generally assumed to be a cofactor in the induction of many cancers, and exposure to pollutants, such as cigarette smoke, is supposed to cause mutation through the combined action of carcinogenic and oxidant chemicals. However, the correlation amongst high oxidation damage and somatic mutation rate in human cells has never been investigated in full for the lack of reliable techniques. In order to study the relation among oxidation damage and mutation rate, we have measured mutation rate by means of the PIG-A gene mutation assay, oxidation damage by the comet assay, and OGG1 activity in peripheral leukocytes of normal healthy subjects, smoking and non-smoking (n=120), and in subjects with squamous cell carcinoma of the head and neck (SCCHN, n=30). The results of a preliminary analysis taking into account the effect of smoking status and of carcinoma on these parameters will be presented.
Measurement of DNA oxidative damage,OGG1 activity and mutation frequency in somatic cells of healthy subjects and patients with head and neck cancer / L. Giovannelli; V. Pitozzi; C. Luceri; E. Bigagli; M. Berardi; T. Rondelli; R. Notaro; P. Dolara. - STAMPA. - 1:(2011), pp. 74-74. (Intervento presentato al convegno 9th International Comet Assay Workshop tenutosi a Kusadasi, Turchia nel 13-16 settembre 2011).
Measurement of DNA oxidative damage,OGG1 activity and mutation frequency in somatic cells of healthy subjects and patients with head and neck cancer
GIOVANNELLI, LISA;PITOZZI, VANESSA;LUCERI, CRISTINA;BIGAGLI, ELISABETTA;DOLARA, PIERO
2011
Abstract
Mutation rate is a key feature of somatic cells which has been difficult to measure in humans. Mutation rate, in association with the number of cell divisions, is likely correlated with the risk of cancer. However, the correlation between mutation rate and cancer has been explored only for rare diseases, like ataxia talangectasia and Fanconi anemia, in which mutation rate is considerably elevated. Oxidation damage is also a key cell pathological event, involved in senescence, inflammation and cancer and inducing loss of function of proteins, lipids, DNA and RNA. In DNA, oxidation damage induces the formation of about twenty different oxidation products, the most important of which is 8-oxodeoxyguanine, which induces code errors and mutations. However, oxidised bases are effectively repaired to conserve DNA integrity, and the presence of a reduced activity of one of the enzymes removing oxidized bases (8-oxoguanosine glycosylases 1, OGG1) is associated with a higher risk of neoplasms, like head and neck cancer. Oxidation damage is generally assumed to be a cofactor in the induction of many cancers, and exposure to pollutants, such as cigarette smoke, is supposed to cause mutation through the combined action of carcinogenic and oxidant chemicals. However, the correlation amongst high oxidation damage and somatic mutation rate in human cells has never been investigated in full for the lack of reliable techniques. In order to study the relation among oxidation damage and mutation rate, we have measured mutation rate by means of the PIG-A gene mutation assay, oxidation damage by the comet assay, and OGG1 activity in peripheral leukocytes of normal healthy subjects, smoking and non-smoking (n=120), and in subjects with squamous cell carcinoma of the head and neck (SCCHN, n=30). The results of a preliminary analysis taking into account the effect of smoking status and of carcinoma on these parameters will be presented.
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