Smoking-induced carcinogenesis

Abstract

Pušenje je jedna od najštetnijih navika te vodeći uzrok karcinoma respiratornih organa, ali i mnogih drugih. Duhanski dim sastoji se od oko 4.700 kemijskih spojeva u koje je uključeno i 50-ak kancerogenih. Kompleksnost duhanskog dima uzrokuje konfuziju u literaturi o mehanizmima kojima karcinogeni induciraju nastanak karcinoma. Dok pojedini autori previše pojednostavljuju mehanizme, odnoseći se prema dimu samo kao katranu ili implicirajući samo na jednu komponentu (B[a]P-7,8-diol-9,10-epoksid), drugi smatraju da su mehanizmi još uvijek nepoznati. U ovom radu prikazan je kratki pregled najvažnijih karcinogena iz duhana te način na koji reagiraju s DNA i uzrokuju genetske promjene, tj. mutacije u onkogenima i tumor supresorskim genima. Naglasak je pritom stavljen na policikličke aromatske ugljikovodike, nitrozamine i aromatske amine koji formiraju DNA adukte kao najvažnije biomarkere u određivanju karcinogenog djelovanja spojeva iz dima. Duhanski dim također je bogat anorganskim kancerogenim tvarima poput metala i slobodnih radikala koji imaju dvojako djelovanje u karcinogenezi, reagirajući direktno s DNA ili indirektno preko drugih spojeva. Najvažniji nekarcinogen u dimu je nikotin. Taj spoj izaziva ovisnost zbog koje osoba nastavlja pušiti unatoč štetnim posljedicama po zdravlje. Iz tog razloga nikotin je glavni „krivac“ što je pušenje postalo glavni uzročnik nastanka raka, tj. 30% svih smrti uzrokovano rakom povezano je s konzumacijom duhanskih proizvoda.Smoking is one of the most harmful habits, and the leading cause of cancer of respiratory organs, and many others. Tobacco smoke consists of approximately 4.700 of chemical compounds which include about 50 carcinogenic. The complexity of cigarette smoke causes confusion in the literature about the mechanisms by which carcinogens induce cancer development. While some authors simplify mechanisms, referring to the smoke just as tar or implying only one component (B[a]P-7,8-diol-9,10-epoxide), others believe that the mechanisms are still unknown. This paper presents a brief overview of the most important tobacco-related carcinogens, and the manner in which they react with DNA and cause genetic changes (mutations) in oncogens and tumor suppressor genes. Emphasis is thereby placed on the polycyclic aromatic hydrocarbons, nitrosamines and aromatic amines that forming DNA adducts as the most important biomarkers in determining the carcinogenic effects of compounds in cigarette smoke. Tobacco smoke also contains large amount of inorganic carcinogens such as metals and free radicals that have a twofold effect in carcinogenesis, reacting directly with DNA or indirectly through other compounds. The most important non-carcinogen in smoke is nicotine. This compound is addictive and person continues to smoke despite the adverse health consequences. For this reason, nicotine is the main "culprit" as smoking has become a major cause of cancer, ie 30% of all deaths caused by cancer is associated with the consumption of tobacco products