While the mutational origin of cancer has increasingly been recognized, the ability to effectively monitor human populations for increased frequency of mutations has been an elusive goal. Two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) has provided the means to analyze a large number of polypeptide gene products simultaneously. Whereas in previous years of funding for this project, the major emphasis was on development of the 2-D PAGE approach for the study of mutation, in this competing renewal application, the major aim is the actual detection of human germinal as well as somatic mutations following exposure to mutagens. We propose to determine the frequency of germinal mutations in cancer patients who have been treated with radiation and chemotherapy and in a control group. The frequency of in vivo somatic mutations will be determined in a group of patients with Hodgkin's disease receiving chemotherapy, before and after therapy, to determine the mutagenic impact of the treatment. In vitro somatic mutation studies will be expanded to include radiation as well as chemical mutagens. For the in vitro studies, the end points to be measured will be facilitated detected in 2-D gels. Scoring of two-dimensional gels will be facilitated by automated image analysis algorithms previously developed and which will undergo further refinement during the funding period.
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