Artikel
The impact of TGF-alpha on tobacco carcinogen induced DNA damage in human mucosal cell cultures
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Autoren
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Philipp Baumeister
- Klinik für Hals-, Nasen- und Ohrenheilkunde, Ludwig-Maximilians-Universität, Munich, Germany
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Maximilan Reiter
- Klinik für Hals-, Nasen- und Ohrenheilkunde, Ludwig-Maximilians-Universität, Munich, Germany
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Sabina Zieger
- Klinisch Experimentelle Onkologie, Klinik für Hals-, Nasen- und Ohrenheilkunde, Munich, Germany
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Ulrich Harréus
- Klinik für Hals-, Nasen- und Ohrenheilkunde, Ludwig-Maximilians-Universität, Munich, Germany
| Veröffentlicht: | 8. Juli 2008 |
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Gliederung
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Introduction: The autocrine stimulatory pathway of cancer cells by transforming growth factor alpha (TGF-α) binding to the epidermal growth factor receptor (EGFR) was shown to be overexpressed in the vast majority of epithelial malignancies including head and neck cancer. This overexpression is also present in histologically healthy mucosa of tumor patients. mRNA levels of both proteins were enhanced in 95% of normal mucosa samples compared to 87,5% of tumor biopsies. This led to the idea, that enhancement of these proteins is an early event in head and neck carcinogenesis [Ref. 1]. Our study was designed to evaluate the effect of growth stimulation on tobacco carcinogen induced DNA damage mimicing the situation of patients years before cancer diagnosis.
Materials and methods: Cell cultures derived from fresh oropharyngeal biopsies of healthy mucosa (tumorpatients and controls) were stimulated with TGF-α 24 h before DNA damage was induced with the tobacco carcinogen benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE). DNA damage was evaluated using the alkaline single cell microgel electrophoresis assay (Comet assay).
Results: After TGF-α stimulation DNA damage decreased significantly in tumorpatients and controls. In tumorpatients DNA damage decreased 38%, in the control group 6%.
Discussion: We found that growth stimulated cells are not more susceptible for DNA reacting agents. On the contrary, TGF-α stimulation had a DNA protective effect, most likely as a consequence of higher chemoresistance induced by growth factor signaling, a well known problem in cancer chemotherapy [Ref. 2].
