Evaluation of genotoxic potential of pemetrexed by using in vitro alkaline comet assay

Abstract

Pemetrexed is a chemotherapeutic drug, approved for the

treatment of mesothelioma and non–small cell lung cancer

and variety of neoplasm. Chemotherapeutic drugs don’t target

only cancer cells in treatment. During treatment these drugs

encounter with normal cells as well. Therefore, in this in vitro

study, it was aimed to investigate the whether genotoxic effect

or not of Pemetrexed on normal leukocytes. In vitro alkaline

comet assay was used in this study. Leukocytes from human

peripheral blood samples from two volunteer donors were

used in the study. In the present study, leukocytes were treated

with four different concentrations (25, 50, 75, and 100 μg/ml)

of the drug for 1 hour. At concentration of 75 μg/ml and 100

μg/ml, there were statistically significant increases in DNA

damage compared to the negative control (p˂0.05, and p˂0.01

respectively). The obtained result shows that Pemetrexed may

have genotoxic potential on normal leucocytes.

Keywords

• Genotoxicity; comet assay; pemetrexed

Pemetrekset’in in vitro Alkali Tek Hücre Jel Elektroforez Yöntemi ile Genotoksik Potansiyelinin Değerlendirilmesi

Abstract

Pemetrekset, mezotelyoma, küçük hücreli olmayan akciğer

kanseri ve pek çok neoplazmın tedavisinde kullanılan

kemoterapötik bir ilaçtır. Kemoterapötik ilaçlar tedavide

sadece kanser hücrelerini hedeflemezler. Tedavi süresince

normal hücrelerde bu ilaçlarla karşılaşırlar. Buradan yola

çıkılarak planlanan bu çalışmada, pemetrekset’in in vitro

koşullarda nomal lökositler üzerine genotoksik etkisinin

olup olmadığının ortaya konulması amaçlandı. Çalışmada,

genotoksisite çalışmalarında hızlı ve güvenilir sonuçlar vermesi

dolayısıyla sıklıkla kullanılan bir yöntem olan alkali tek hücre

jel elektroforez yöntemi kullanıldı. İki gönüllü donörden alınan

insan periferal kan örneklerinden elde edilen lökositler, ilacın

dört farklı konsantrasyonu (25, 50, 75 ve 100μg/mL) ile 1 saat

muamele edildi. DNA hasarı bakımından 75μg/mL (p˂0,05) ve

100μg/ml’de (p˂0,01) negatif kontrole göre istatistiksel olarak

anlamlı bir artış tespit edildi. Bu bulgu, pemetrekset’in normal

lökositler üzerine genotoksik potansiyelinin olabileceğini

göstermektedir.

Keywords

• Genotoksisite; tek hücre jel elektroforez yöntemi; pemetrekset

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