334
when bind to DNA cause transformation of normal cells to malignant one [77, 78].
It has been confirmed that food prepared at high temperatures (such as barbecuing
or grilling) results in high levels of PAHs. The interest and consequences related
with PAHs have been increased because of their capability to hamper the activity of
hormone metabolizing enzymes which results in harmful effects on the reproduction as well as immunity [79, 80].
PAHs and Carcinogenic Pathways
In general, PAHs belong to lipophilic compounds which have the property to easily
cross plasma membranes via passive diffusion post-inhalation, ingestion, or skin
contact. PAHs parental molecules that gain access are considered pro-carcinogens
because they cause an indirect damage to DNA molecule [81–83]. Instead, transformed carcinogenic metabolite of a single PAH contributes to cancer etiology. This
transformation involves various metabolic enzymes which mostly follow three
known pathways: the CYP/EH pathway (CYP1A1/1B1 and epoxide hydrolase
pathway), CYP peroxidase pathway, and AKR pathway (aldo-keto reductases pathway). Generally, metabolic enzymes such as CYPs metabolize PAHs into quinones,
phenols, and catechols which results in diol epoxides, radical cations, or reactive
and redox-active o-quinones formation, which further reacts with DNA to form
DNA adducts. For instance, quinones react with the N-3 of adenine and N-7 of guanine of DNA [84]. These DNA adducts result in incompatibility in DNA duplication, transformed promoter methylation as well as promoter binding [85] and hence
leads to hereditary DNA mutation or atypical gene expression level, which ultimately results in cancer development. Though PAHs are supposed not to cause
hepato cancer, but they are break down to reactive DNA metabolites in hepatocytes
subsequent oral consumption [45]. PAHs reactive metabolites also enhance protein
adduction in cells [86, 87], which further regulate the usual function of the proteins.
PAH metabolites also result in increased production of reactive oxygen species
(ROS), which directly damages the structure of DNA, lipids, or proteins and thus
initiates carcinogenesis [88].
Tests Used to Determine the Biological Activity of PAHs
The following are some of the assays which are very commonly used to evaluate the
biological effect of PAHs especially ePAHs from various samples.
A. Khan et al.
when bind to DNA cause transformation of normal cells to malignant one [77, 78].
It has been confirmed that food prepared at high temperatures (such as barbecuing
or grilling) results in high levels of PAHs. The interest and consequences related
with PAHs have been increased because of their capability to hamper the activity of
hormone metabolizing enzymes which results in harmful effects on the reproduction as well as immunity [79, 80].
PAHs and Carcinogenic Pathways
In general, PAHs belong to lipophilic compounds which have the property to easily
cross plasma membranes via passive diffusion post-inhalation, ingestion, or skin
contact. PAHs parental molecules that gain access are considered pro-carcinogens
because they cause an indirect damage to DNA molecule [81–83]. Instead, transformed carcinogenic metabolite of a single PAH contributes to cancer etiology. This
transformation involves various metabolic enzymes which mostly follow three
known pathways: the CYP/EH pathway (CYP1A1/1B1 and epoxide hydrolase
pathway), CYP peroxidase pathway, and AKR pathway (aldo-keto reductases pathway). Generally, metabolic enzymes such as CYPs metabolize PAHs into quinones,
phenols, and catechols which results in diol epoxides, radical cations, or reactive
and redox-active o-quinones formation, which further reacts with DNA to form
DNA adducts. For instance, quinones react with the N-3 of adenine and N-7 of guanine of DNA [84]. These DNA adducts result in incompatibility in DNA duplication, transformed promoter methylation as well as promoter binding [85] and hence
leads to hereditary DNA mutation or atypical gene expression level, which ultimately results in cancer development. Though PAHs are supposed not to cause
hepato cancer, but they are break down to reactive DNA metabolites in hepatocytes
subsequent oral consumption [45]. PAHs reactive metabolites also enhance protein
adduction in cells [86, 87], which further regulate the usual function of the proteins.
PAH metabolites also result in increased production of reactive oxygen species
(ROS), which directly damages the structure of DNA, lipids, or proteins and thus
initiates carcinogenesis [88].
Tests Used to Determine the Biological Activity of PAHs
The following are some of the assays which are very commonly used to evaluate the
biological effect of PAHs especially ePAHs from various samples.
A. Khan et al.