Genotype-phenotype association of TGF-pi and GST with chemo-radiotherapy induced toxicity

Background: Normal tissue toxicity continues to remain as a major challenge for radiation oncologists for delivering the total dose to the tumour cells in cancer patients. Cellular, molecular and plasma based early biomarkers to predict the overreactions and non-overreactions of normal tissue toxicity before the initiation of radiotherapy can be valuable for personalised treatment. The aim of the current study was to analyse the interrelationship between polymorphisms in Glutathione S- Transferases [GSTs] and Transforming Growth Factor-pi [TGF-J31], the plasma level/activity of these proteins with the development of chemo-radiotherapy induced oral mucositis and skin reaction in head and neck cancer [HNC] patients

Materials and Methods: We analysed polymorphisms in TGF-fil and GST by restriction digestion of the PCR amplified products and we also assessed circulating TGF-pl levels and GST activity by Enzyme Linked Immunosorbent Assay [ELISA]

Results: The results indicate that pre-radiotherapy plasma TGF-P1 levels and total GST activity has no correlation with radiation induced normal tissue skin reaction and oral mucositis in HNC patients

Conclusion: The selected polymorphisms in TGF-fil and GST had no influence on TGF-P1 levels and total GST activity. Plasma TGF-P1 and GST activity was not affected by the presence of selected polymorphisms and lacks significance in predicting skin reaction and oral mucositis prior to chemo-radiotherapy

Induction of micronuclei in a transplantable murine tumor after multimodality treatment with cis-platin, radiation and hyperthermia

Tumor response after multimodality treatment using combination of radiation, chemotherapeutic drugs and hyperthermia usually assessed by parameters such as tumor growth delay, volume doubling time and regression response. The study herein was conducted to investigate the usefulness of micronucleus assay for assessing the multimodality treatment. The induction of micronuclei [MN] in a transplantable solid tumor grown in inbred Balb/c mice was analyzed after treating the tumors with cis-platin [cDDP], radiation [RT] and hyperthermia [HT]. The MN frequency in tumor was measured at 1, 3, 5 and 7 days of post-treatment. On day 1, all the cDDP and RT groups, except HT treatment produced significantly higher MN counts from that of the untreated tumors. Cis-platin treatment resulted in a dose-dependent linear increase in the frequency of MN induction on day one. Combination of radiation with cDDP or HT, as bimodality treatment further increased the MN counts. In the tri-modality group [cDDP+RT+HT] the MN counts were not significantly higher than the bi-modality treatments, however there was an immediate tumor shrinkage indicating the contribution of other forms of cell death. Although, MN counts were declined after day five post-treatment, remained significantly higher than the control on day seven-post treatment in hyperthermia alone or its combination with RT and RT+ cDDP groups. Micronucleus assay may be useful for assessing the post-treatment regression response of resistant tumors, while monitoring the response of sensitive tumors the parameters such as apoptosis and necrosis may also contribute considerably to tumor cell loss contributing immediate tumor regression