Biotransformation of benzo[a]pyrene (BaP) in the presence of microsomal fractions derived from liver and epiderm of adult and WEANLING RATs was examined. The aim of this study was to evaluate the effect of age on the capacity of two organs in transformation of BaP. Subcellular fractions were prepared from skin and liver by ultracentrifugation and were used as the source of BaP metabolizing enzymes in a reconstitution assay system. Microsomal fractions are sources of cytochrome P-450 and cytosols are the source of glutathione Stransferase (GST). In a metabolic activation assay system, cytochrome P-450 catalyses the formation of reactive epoxide of BaP which can then interact with exogenous DNA. Adult RAT liver microsomes with the highest cytochrome P-450 and maximum capacity for BaP-DNA adducts formation (~204 pmol BaP bound/mg DNA) are considered as positive control in this assay system. The adduct formation in the presence of adult and young RATs was approximately 204 and 27 pmol/mg DNA, respectively. Microsomes prepared from skin samples of adult and young RATs mediated approximately 49 and 16 pmol BaP binding to DNA respectively. With the addition of cytosol to the microsome-mediated system an in vitro detoxification model has been established. The results obtained by the addition of different cytosolic samples showed that liver cytosol which contains highest GST activity caused about 28% inhibition in BaP binding to DNA. The inhibitory effects of cytosolic fraction from WEANLING liver, adult skin and WEANLING skin were 17, 19 and ~9% respectively. These data show that isolated subcellular fractions from young RATs are less efficient in the biotansformation of BaP. However, the results obtained in vitro do not reflect the changes in vivo. Further, in vivo experiments should be carried out after BaP administRATion to animals to confirm the differences in the BaP-DNA adduct formation and BaP-glutathione conjunction in tissues of young and adult animals.

Purpose: The aim of this study was to evaluate the effect of age on the capacity of liver and epiderm of adult and weanging RATs in transformation of Benzo (α) Pyrene.Materials and Methods: In a metabolic activiation assay system, cytochorome P-50 (from microsomal fraction) catalyses the formation of reactive epoxide of BaP which can then interact with exogenous DNA The capacity of cytochrome P-450 for BαP-DNA adducts formation from different organs are adult RAT live>>> adult RAT skin>> weanging RAT liver> WEANLING RAT skin. With the addition of cytosol (the source of glutathione S transferase (GST) to the microsome-mediated system an In vitro detoxification model has been established.Results: The results obtained by the addition of different cytosolic samples are shown in several tables in the text. These data show that isolation of subcellular fractions from young RATs are less efficient in the biotransformation of BαP and detoxification by GSH is a passive process that depends on activation process. Also metabolic activation of BaP with cytochorome P-450 is not the first degree with glutathione detoxification. However, the results obtined In vitro do not reflect the exact change In vivo.

Objectives: To compare aflatoxine B1 effect as a carcinogen by activation and development of liver metabolite enzymes and amount of binding of aflatoxine B1 with DNA in infant RATs. Materials and Methods: In this research, enzyme activation and variation after burning are exposed. Infant RAT liver capability for exchanging AFB1 to Epo-Oxide activator form and amount of binding of [3H] AFB1 Epo-Oxide to DNA in "Inviter form" in the presence of variable aged liver microsoems were measured. Results: This study shows that the acieRATion of AFB) metabolite enzymes before adult ages is lower and a description difference is observed. Additionally, [3H] AFB1 binding to DNA in infant RATs are less than adult RATs. Conclusion: Results of this study show that in fant RAT liver has less capacity for exotoxic and exocarcinogen metabolism such as aflatoxine B1 and result in deposition and exhaustion of mentioned material in their bodies which may eventually expose them to cancer.      

Benzo (a) Pyrene is a carcinogen polycyclic aromatic hydrocarbon which diffuses into the environment from combustion of organic materials. Based on various epidemiological evidences it is related to lung, skin and liver cancer. Mutagen city, and immunosuppressivity are among important biological effects of Benzo (a) pyrene. After absorbtion and distribution in the body, it undergoes epoxidation by cytochrome P-450 system in the cells. Some of the electrophilic metabolites covalently bind to cellular macromolecules and in particular to DNA. Its metabolites are partially detoxified by conjunction to cellular glutathione (GSH), glucoronic acid, and sulphate. Biological effects of B (a) P and its metabolits depend on various factors such as species, age, sex, tissue, diet, dose, genetic system, etc. The fundamental physiological differences between newborns and adults are variations in susceptibility to chemical carcinogens observed between the two age groups. In this paper we studied the level of binding of B (a) P to calf thymus DNA and formation of DNA adduct in the incubation systems which contained adult and newborn RAT liver and skin microsomes. Results indicate that in both age groups liver microsomes in comparison to skin microsomes cause a higher increase in the level of DNA adduct and the RATio of DNA adduct in the liver of adults compared to animal skin was 4.2 to 1. The quantity of adduct in the incubation systems containing liver microsomes of newborn was 1.51 higher than that of skin microsomes. Moreover phenobarbiton failed to induce cytochrome P-450 and any increase in DNA adduct level of B (a) P in the newborns RAT. The level of cytochrome P-450 in adults liver was 2.86 times higher than that in newborns' liver.

Previous studies demonstRATed that CSE induces oxidative stress and its consequences on isolated mitochondria obtained from lung, heart and brain which may provide insight into the role of CSE in human health and disease. The present study was carried out to further characterize and compare toxic effect of CSE extract on isolated mitochondria obtained from either a directly contacting tissue (i. e. skin) or a vital visceral tissue (i. e. liver). We obtained RAT liver and skin mitochondria by differential ultracentrifugation and incubated the isolated mitochondria with different concentRATions (1, 10 and 100%) ofstandardizedcigarette smoke extract (CSE). Our results were similar to our previous study which discovered CSE toxicity mechanisms on isolated mitochondria obtained from lung, heart and brain with minor changes. CSE induced a significant rise in ROS formation, lipid peroxidation and mitochondrial membrane potential collapse and mitochondrial swelling on isolated mitochondria obtained from both liver and skin. CSE induced Decrease in ATP concentRATion on isolated mitochondria obtained from both liver and skin did not include CSE lowest concentRATion (1%). Our findingsshowed that CSEinduced toxicity in liver and skin is due to disruptive effect on mitochondrial respiRATory chain which canleads to cytochrome c release and apoptosis signaling.