الفهرس 
INTRODUCTION AND AIM OF THE WORKOnly 14 pages are availabe for public view
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Abstract
Tobacco smoking is the most popular form of smoking and is practiced by over one billion people in the majority of all human societies.
Marijuana (cannabis) is the most widely used illegal drug worldwide and is considered as the second most commonly smoked substance after tobacco.
There is a strong link between consumption of cannabis and tobacco smoking as the majority of cannabis users also tobacco smokers. The concomitant use of cannabis and tobacco is of concern. Cannabis use promotes the transition to more profound tobacco smoking and to make it more difficult to quite tobacco smoking.
Oxidative stress is a situation when steady-state reactive oxygen species (ROS) concentration is transiently or chronically enhanced, disturbing cellular metabolism and its regulation and damaging cellular constituents. It is also defined as a situation of imbalance between the ROS and the availability and the activity of antioxidants. Disturbance of this balance is attributed to increased generation of free radicals or decreased antioxidant activity.
Tobacco and marijuana smoking has considerable potential for inducing oxidative modifications and depletion of antioxidants. Oxidative damage to lipids, proteins, and DNA by smoke-derived ROS has been extensively demonstrated.
Telomeres are long repetitive DNA sequences of TTAGGG located at the end of the linear chromosomes and bound by shelterin proteins. Shelterin proteins function as the protection for the loop structure of telomere, which prevents the activation of DNA damage response at the chromosome ends and activates DNA repair mechanism.
Telomeres have different functions including capping the end of the chromosomes, protecting them from end-to-end fusion and from being recognized as double strand breaks in the genome and ensuring genome stability.
Three major mechanisms which influence the telomere length are the end-replication problem, the action of C-strand-specific exonuclease and oxidative DNA damage induced by environmental and occupational risk factors. However, oxidative stress has been shown to be the major mechanism which can influence the telomere length.
The present study was conducted to investigate the effect of tobacco and marijuana smoking on leukocyte telomere length and oxidative stress.
It was carried out on 90 Egyptian male subjects. They were divided into three groups matched for age (25-55years) and socioeconomic status.
group I included 30 non smokers (non tobacco, non marijuana smokers) as a control group.
group II consisted of 30 tobacco smokers.
group III comprised 30 tobacco and marijuana smokers.
Consent was taken from all participants then all the included subjects were interviewed to fill a questionnaire, including personal, medical and smoking histories.
All of the participants were free of serious illness, including infectious diseases, cardiovascular diseases, mental disorders, and cancer, at the time of participation.
Blood was aspirated from each individual for the determination of leukocyte telomere length (LTL), malondialdehyde (MDA) as a marker of oxidative stress and total antioxidant capacity (TAC).
Urine sample was collected from each individual for the determination of levels of urinary 8-hydroxydeoxyguanosine (8-OHdG), as a biomarker of oxidative DNA damage, cotinine as a biomarker of tobacco smoking and delta-9-tetrahydrocannabinol (THC) as a biomarker of marijuana smoking.
Parameters of the study were measured by:
• Leukocyte telomere length was measured using qPCR-based technique.
• Oxidative markers like malondialdehyde was measured spectrophotometrically.
• The total antioxidant capacity was measured spectrophotometrically.
• Levels of the urinary 8-OHdG as a biomarker of oxidative DNA damage was measured using HPLC.
• Cotinine as a biomarker of tobacco smoking was measured by ELISA.
• Tetrahydrocannibinol (THC) as a biomarker of marijuana smoking was measured by enzyme immunoassay.
In the present study the levels of MDA which is a product produced as a result of lipid peroxidation were significantly increased in both group II(tobacco smokers)and group III(tobacco and marijuana smokers) as compared to group I (control group).
The levels of 8-Hydroxydeoxyguanosine (8-OHdG) were significantly increased in group II (tobacco smokers) and group III (tobacco and marijuana smokers) as compared to group I (control group).
The levels of total antioxidant capacity (TAC) were significantly decreased in both group II (tobacco smokers) and group III (tobacco and marijuana smokers) as compared to group I(control group).
The association between oxidative stress and increased rate of telomeric shortening is mostly occur as a result of direct ROS-induced damage to telomeric DNA.
The comparison between the three groups as regards leukocyte telomere length (T/S ratio)showed significant decrease in leukocyte telomere length (T/S ratio) of group II(tobacco smokers) and group III (tobacco and marijuana smokers) when compared to group I(control group).Also by comparison between different age categories there was a decrease in leukocyte telomere length (T/S ratio) by increase in age which means that long term smoking of tobacco alone or tobacco and marijuana led to shortening of the leucocyte telomere length.
from the previous findings either tobacco smoking or tobacco and marijuana smoking induces oxidative stress, DNA damage and shortening of leucocyte telomere length which accelerate aging and predispose to cancer and multiple diseases.