Utjecaj progesterona na toksičnost benzena u štakora

Benzene is a frequently used industrial solvent. Its toxic manifestations could be modified by sex hormones, but mechanisms of their action are poorly understood. We have examined the influence of progesterone on lipid peroxidation (malondialdehyde), reduced glutathione (GSH), and cytochrome P450 2E1 (CYP2E1) in the liver and kidneys of female rats. Progesterone applied to benzene-treated rats inhibited the formation of reactive oxygen species (ROS), but in ovariectomised benzene-treated rats it significantly increased GSH in the liver. No improvement in CYP2E1 activity was observed in progesterone treated rats. Our results evidence that progesterone changes benzene toxicity (generation of ROS, oxidative stress). However, the probable antioxidative effect of progesterone needs to be confirmed by further studies.Benzen se u industriji često rabi kao otapalo. Zna se da na njegovu toksičnost mogu utjecati spolni hormoni, ali su mehanizmi njihova djelovanja još uvijek slabo poznati. Ispitali smo utjecaj progesterona na peroksidaciju lipida (malondialdehida), pad razina glutationa te aktivnost citokroma P450 2E1 (CYP2E1) u jetri i bubrezima štakorica. Primjena progesterona u štakorica koje su prethodno primile benzen inhibirala je stvaranje reaktivnih molekula kisika (engl. reactive oxygen species, krat. ROS), ali je u štakorica s ovariektomijom koje su također primile benzen doveo do značajnoga rasta glutationa u jetri. U štakorica koje su primile progesteron nije zamijećena poboljšana aktivnost izoeznima CYP2E1. Naši rezultati potvrđuju da progesteron utječe na toksičnost benzena (stvaranje ROS-a i oksidativni stres). Međutim, tek u budućim istraživanjima valja potvrditi djeluje li progesteron antioksidativno

HIFα as a target for different oncoproteins during carcinogenesis

The basic characteristics of tumours are ability for invasiveness and metastasis. These properties are realized due to destruction of intercellular matrix caused with acidification of intercellular area stimulated with transition from tissue respiration to glycolysis. The transition  to glycolysis in tumor cells is observed not only during hypoxic state how is realized in normal cells but also during oxygenation (Warburg  effect). It is accepted that by any carcinogenic action the activation of oncogenes or inactivation of genes – supressors occurs. As a result  it is permanent expression of oncoproteins and stimulation of tumour development. Different oncoproteins operate in different regulation systems at that they cause the same effect – tumour development.It is assumed that oncoproteins are not the ultimate factor in tumour development but there are existed some common element which is activated by different oncoproteins. In this review it is assumed that common element is HIFα (hypoxia-inducible factor α) transcription factor and it is discussed the mechanisms its activation by oncoproteins takes place in different signal systems

HIFα как объект воздействия различных онкобелков при канцерогенезе

The basic characteristics of tumours are ability for invasiveness and metastasis. These properties are realized due to destruction of intercellular matrix caused with acidification of intercellular area stimulated with transition from tissue respiration to glycolysis. The transition  to glycolysis in tumor cells is observed not only during hypoxic state how is realized in normal cells but also during oxygenation (Warburg  effect). It is accepted that by any carcinogenic action the activation of oncogenes or inactivation of genes – supressors occurs. As a result  it is permanent expression of oncoproteins and stimulation of tumour development. Different oncoproteins operate in different regulation systems at that they cause the same effect – tumour development.It is assumed that oncoproteins are not the ultimate factor in tumour development but there are existed some common element which is activated by different oncoproteins. In this review it is assumed that common element is HIFα (hypoxia-inducible factor α) transcription factor and it is discussed the mechanisms its activation by oncoproteins takes place in different signal systems.Основные свойства злокачественности – инвазия и метастазирование – реализуются благодаря разрушению межклеточного матрикса. В этом процессе принимают участие металлопротеазы, активация которых вызвана подкислением межклеточного пространства, обусловленного переходом опухолевых клеток с тканевого дыхания на гликолиз. Переключение на гликолиз в опухолевых клетках происходит не только в условиях гипоксии, что наблюдается и в нормальной ткани, но и при оксигенации (эффект Варбурга). Считается, что в процессе канцерогенеза происходит активация онкогенов и / или дезактивация генов-супрессоров, вызывающие в конечном итоге развитие опухоли. Трансформация и последующая пролиферация клеток опосредована функциональным действием целого ряда онкобелков, являющихся компонентами различных регуляторных сигнальных цепей. Можно предположить, что онкобелки не всегда конечные факторы, вызывающие развитие опухолевого процесса, а конечным звеном является некий общий для всех канцерогенных воздействий элемент, активируемый различными онкогенами.В данном обзоре обсуждается возможность того, что при функционировании многих онкогенных факторов таким звеном является транскрипционный фактор HIFα (hypoxia-inducible factor α), и рассматриваются механизмы его активации при действии онкогенов, участвующих в регуляции различных сигнальных систем