BioProject

The uncovering of genes involved in susceptibility to the sporadic cancer types is a great challenge. More...

The uncovering of genes involved in susceptibility to the sporadic cancer types is a great challenge. It is well established that the way in which an individual deals with DNA damage is related to the chance to develop cancer. Mutagen sensitivity is a phenotype that reflects an individual’s susceptibility to the major sporadic cancer types, including colon, lung and head and neck cancer. A standard test for mutagen sensitivity is measuring the number of chromatid breaks in lymphocytes after exposure to bleomycin. The aim of the present study was to search for the pathways involved in mutagen sensitivity. Lymphoblastoid cell lines of seven individuals with a low mutagen sensitivity were compared with seven with a high score. RNA was isolated from cells exposed to bleomycin (4 hr) and unexposed cells. Micro-array analysis (19K) was used to compare gene expression of insensitive and sensitive cells. The profile of most altered genes after bleomycin exposure, analyzed in all fourteen cell lines, included genes involved in multiple processes, most prominent in cell proliferation and DNA repair. When comparing the insensitive and sensitive individuals other differentially expressed genes were found, that were involved in proliferation (e.g. BUB1) and signal transduction (e.g. DUSP4). This difference in expression profiles between mutagen sensitive and insensitive individuals justifies further studies aiming to elucidate the genes responsible for the development of sporadic cancers. Keywords: exposure to dna damaging agent, comparison of phenotypic response to dna damaging agent Overall design: We analyzed 14 lymphoblastoid cell lines without and with exposure to bleomycin for 4hr. Seven of these fourteen were insensitive to bleomycin, meaning that few chromatide breaks were examined after exposure to bleomycin. The other seven were sensitive, meaning that in these cell lines a relatively high number of chromatide breaks could be detected after exposure to bleomcyin. Less...