Dimethyl isophthalate (DMIP)'in in vitro ve in vivo toksik etkileri ve nörotoksisite potansiyeli

Fitalatlar, temel olarak çok çeşitli ürünler ve uygulamalara esneklik, şeffaflık, dayanıklılık ve uzun ömür katması için plastikleştirici ajanlar olarak kullanılan fitalik asit esterleridir. Başlıca tibbi cihazlar, kozmetik ürünler, emülsifiye edici ajanlar, oyuncaklar ve yapıştırıcılarda kullanılmaktadırlar. Fitalatlar plastik madde ile kovalent olarak bağlanmadığından kolaylıkla çevreye yayılabilirler. Dimetil İzofitalat (DMIP) parfüm fiksatifi ve polyester reçineleri yapmak için plastikleştirici olarak kullanılmaktadır. DMIP'nin toksisitesi ile ilgili herhangi bir bilgi bulunmamaktadır. Bu çalışmada DMIP'nin in vitro genotoksik ve sitotoksik etkilerinin belirlenmesinin ardından, ex-vivo denemeler uygulanmış daha sonra in vivo akut ve subakut toksisite testi uygulanarak toksik ve nörotoksik etkilerinin incelenmesi amaçlanmıştır. Tek doz akut toksisite denemesi sonucunda hesaplanan LD50 değeri dikkate alınarak, 28 günlük tekrarlı doz toksisite denemesinde DMIP, 28 gün boyunca haftada 5 gün olacak şekilde aynı saatte farelere oral olarak uygulanmış ve deneme sonunda biyokimyasal ve histolojik parametreler incelenmiştir. Sonuç olarak bu tez çalışması ile elde edilmiş olan tüm toksisite verileri doğrultusunda, DMIP'nin sitotoksisite ve akut doz denemelerinde toksik olmadığı ancak AMES testi sonucu ile genotoksik olduğu, ex-vivo ve subakut toksisite denemelerine göre toksik olduğu ilk kez ortaya konmuştur.Phthalates are esters of phthalic acid and are mainly used as plasticizers in a wide variety of products and applications which are added to plastics to increase their flexibility, transparency, durability, and longevity. They are mainly used in medical devices, cosmetics, emulsifying agents, toys and adhesives. Phthalates are not covalently bound to the plastic material and can easily leach into the environment. Dimethyl Isophthalate (DMIP) is used as a perfume fixative and as a plasticizer to make polyester resins. There is no information on DMIP toxicity. In this study, in vitro genotoxic and cytotoxic effects of DMIP were determined, ex-vivo assays were performed and then toxic and neurotoxic effects were investigated by in vivo acute and subacute toxicity tests. After single dose acute toxicity test LD50 value is calculated and with this value we start to 28 days subacute toxicity test with DMIP which is orally administered to mice 28 days, 5 days per week at the same time each day and at the end of the experiment biochemical and histological parameters were examined. In conclusion, with the toxicity data obtained from this study it is for the first time revealed that DMIP has not been found toxic in cytotoxicity and acute dose assays but it has been found to be a genotoxic substance that by AMES test results and a toxic substance in ex-vivo and subacute toxicity assays

Prognostic and predictive role of liquid biopsy in lung cancer patients

IntroductionLung cancer (LC) is a leading cause of cancer-related mortality worldwide. Approximately 80% of LC cases are of the non-small cell lung cancer (NSCLC) type, and approximately two-thirds of these cases are diagnosed in advanced stages. Only systemic treatment methods can be applied to patients in the advanced stages when there is no chance of surgical treatment. Identification of mutations that cause LC is of vital importance in determining appropriate treatment methods. New noninvasive methods are needed to repeat and monitor these molecular analyses. In this regard, liquid biopsy (LB) is the most promising method. This study aimed to determine the effectiveness of LB in detecting EGFR executive gene mutations that cause LC.MethodsOne hundred forty-six patients in stages IIIB and IV diagnosed with non-squamous cell non-small cell LC were included. Liquid biopsy was performed as a routine procedure in cases where no mutation was detected in solid tissue or in cases with progression after targeted therapy. Liquid biopsy samples were also obtained for the second time from 10 patients who showed progression under the applied treatment. Mutation analyses were performed using the Cobas® EGFR Test, a real-time PCR test designed to detect mutations in exons 18, 20, and 21 and changes in exon 19 of the EGFR gene.ResultsMutation positivity in paraffin blocks was 21.9%, whereas it was 32.2% in LB. Solids and LB were compatible in 16 patients. Additionally, while no mutation was found in solid tissue in the evaluation of 27 cases, it was detected in LB. It has been observed that new mutations can be detected not only at the time of diagnosis, but also in LB samples taken during the follow-up period, leading to the determination of targeted therapy.DiscussionThe results showed that “liquid biopsy” is a successful and alternative non-invasive method for detecting cancer-causing executive mutations, given the limitations of conventional biopsies.</jats:sec