Metabolic activation and DNA adduct formation of Benzo(a) pyrene by adult and newborn rat skin and liver microsomes

Document Type: Original Article

Authors

1 Instructor

2 Assistant professor

3 Associate professor

Abstract

Benzo(a) pyrene is a carcinigen polycyclic aromatic hydrocarbon which diffuses into the environment from combustion of organic meterials.based on various epidemiological evidences it is related to lung,skin and liver cancer.mutagenicity,and immunosuppressivety 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 conjunction to cellular glutathione (GSH),glucoronic acid,and sulphate.biological effects of B(a) P and its metabolits depent on various factors such as species,age,sex,tissue,diet,dose,genetic system,etc.the fundemental physiological difference 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 adilt 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 addult and the ratio of DNA aduct in the liver of adults compared to animal skin was 4.2 to 1.the quatity 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 adult liver was 2.86 times higher than that in newborns, liver.

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