Abstract
The carcinogen 7,12-dimethylbenz(a)anthracene (DMBA) is a model of Polyaromatic hydrocarbons (PAHs) which is metabolized to DMBA-trans-3,4-diol, an intermediate inductive of DNA mutations through alteration of DNA base pairs, initiation of chronic inflammation and excessive production of Reactive Oxygen Species which is very toxic substances in tissue. This study was aimed to investigate the preventive effects of Melatonin. DNA damage was induced by topical treatment of DMBA to the shaven part of mice skin. Animals injected with melatonin (10 mg/kg ) intraperitoneally. mice bone marrow cells were used for the determination of chromosomal aberrations, micronuclei and the percentage of mitotic index. DMBA induced significant elevations in structural chromosome abnormalities, micronuclei, and caused a significant decreases in the mitotic index. The pre-treatment group (Me + DMBA) greatly reduced the number of CA and enhanced MI frequency compared to DMBA treated animals. statistical analysis showed that the number of induced Di-MN and Tri –MN in pre and post treatment groups were decreased significantly compared with the positive control.
Highlights
Melatonin may enhance cellular defenses against oxidative stress of antioxidant enzymes such as glutathione peroxidase, catalase and superoxide dismutase [21], all leading to a decrease in DNA damage by interacting with double-stranded DNA and promoting its stability and integrity [35, 25] .On the other hand, (DMBA) has been shown to induce mutations, It is metabolized by epidermal Langerhans cells to DMBA-trans-3,4-diol, an intermediate inductive of DNA mutations through alteration of DNA base pairs, initiation of chronic inflammation and excessive generation of (ROS),(20,34),which in turn participates in transforming the normal cells to malignant pathways [26,6]
Effect of melatonin on mitotic index and with melatonin for another 14 days after chromosome aberrations induced by DMBA: applying DMBA on the dorsal shaved part of
The slide analysis of a mouse bone marrow the mouse, showed that chromosome breaks smear from the negative control animals and chromatid breaks not affected significantly revealed a frequency of 7 types of by melatonin treatment,while melatonin chromosomal aberrations from 500 analyzed acted its protecting effect on both chromosome cells, the dicentric chromosome, chromosome fragment and chromosome gaps . this fragment and gaps recorded the highest treatment reveals a reduction in the total aberrant value,Total aberrations was (364.7) number of aberrations(656.0)
Summary
Melatonin is N-acetyl 5 methoxytryptamine, which is a mammalian pineal gland hormone, but it is known to be synthesized in different other organs, tissues, and cells [23] Melatonin is critical for the regulation of circadian and seasonal changes in various aspects of physiology, neuroendocrine functions [15], In addition to its anti-tumor and oncostatic activity [4,28] and ability to stimulate the immune system, apart from the above functions; melatonin possesses strong antioxidant activity by which it protects cells, tissues and organs from the oxidative damage [17] Many melatonin receptors are found in the body which explains its multiple biological functions, acting both centrally and peripherally in a wide variety of target systems [5], via its receptors, melatonin exerts effects on the secretion of various other hormones, either directly or indirectly by influencing the circadian multioscillator system [10]. The objective of this study was undertaken to evaluate the effects of melatonin against the genotoxicity induced by DMBA in mice bone marrow cells using the chromosomal aberrations, mitotic index and micronucleus test as a dependent cytogenetic endpoints. Animals of the second group, the positive control were applied once topically to the shaven part of mice skin with 0.5 ml of DMBA (100 mg/100 mL of acetone). Group five: (PostDMBA treatment) animals treated with a single dose of DMBA once (1 day) and administrated with melatonin 10 mg/kg for 14 consecutive days. 2013) and analyzed using one – way ANOVA observed when the animals were injected with according to the following model : Yij = M + melatonin 14 consecutive days before treating
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