330
meat products also contain significant quantity (0.1–20 mg/kg; up to 100 mg/kg) of
PAHs [31–33].
Effect of PAHs on Various Enzymatic and Metabolic Pathways
Most aryl hydrocarbon receptor (AhR) is stimulated by PAH isomers which principally act as an activator to stimulate various biochemical and toxic responses,
including the regulation of cytochromes P450 (1A1 and 1B1), which leads to toxic
transformation of the cell and thus develop cancer [34–36]. Moreover, some PAHs
affect endocrine system by inducing ovarian estrogen receptor b expression and
peroxisome proliferator-activated receptor alpha (PPARa) and delta (PPARb/d) activation. TCA cycle and purine metabolism are highly disturbed due to PAH exposure
[37–39].
Excessive exposure of PAHs mostly causes lung cancer, resulted due to induction of metabolic enzymes including cytochrome P450 (CYP) monooxygenases, i.e.
CYP1A1/2 and 1B1, and phase II enzymes including aldo-keto reductases (AKRs),
NADPH quinone oxidoreductases (NQOs), UDP glucuronyl transferases, glutathione S-transferases, and epoxide hydrolases (EHs), by entering into the lungs via
aryl hydrocarbon receptor (AhR)-dependent and independent pathways. PAHs
metabolism produce active carcinogens, diol epoxides, radical cations, and
o- quinones using CYP1A1/1B1/EH, CYP peroxidase, and AKR pathways which
leads to produce reactive DNA adducts, results in DNA mutations and change in the
downstream gene expression profile, ultimately leads to the development of cancer.
Mutations in xenobiotic metabolic enzymes, tumor suppressor genes (e.g. p53) and
genes responsible for cancer susceptibility from various age groups, ethnicities, and
gender [40].
Endocrine and Endocrine Disruptors
In the regulation of fats, carbohydrates, and proteins metabolism, endocrine system
plays a crucial role to provide fuel to the body in the form of energy, all the times.
When the availability is more, endocrine hormones are accountable to mobilize and
store excess energy in the form of fats in various parts of the body. During scarcity
or unavailability of energy sources, this stored energy is mobilized again to compensate need of the body and most importantly to maintain constant blood glucose
level. An imbalance between these two processes occurs whenever there is change
in hormones secretion or production to drive the processes of metabolism.
A. Khan et al.
meat products also contain significant quantity (0.1–20 mg/kg; up to 100 mg/kg) of
PAHs [31–33].
Effect of PAHs on Various Enzymatic and Metabolic Pathways
Most aryl hydrocarbon receptor (AhR) is stimulated by PAH isomers which principally act as an activator to stimulate various biochemical and toxic responses,
including the regulation of cytochromes P450 (1A1 and 1B1), which leads to toxic
transformation of the cell and thus develop cancer [34–36]. Moreover, some PAHs
affect endocrine system by inducing ovarian estrogen receptor b expression and
peroxisome proliferator-activated receptor alpha (PPARa) and delta (PPARb/d) activation. TCA cycle and purine metabolism are highly disturbed due to PAH exposure
[37–39].
Excessive exposure of PAHs mostly causes lung cancer, resulted due to induction of metabolic enzymes including cytochrome P450 (CYP) monooxygenases, i.e.
CYP1A1/2 and 1B1, and phase II enzymes including aldo-keto reductases (AKRs),
NADPH quinone oxidoreductases (NQOs), UDP glucuronyl transferases, glutathione S-transferases, and epoxide hydrolases (EHs), by entering into the lungs via
aryl hydrocarbon receptor (AhR)-dependent and independent pathways. PAHs
metabolism produce active carcinogens, diol epoxides, radical cations, and
o- quinones using CYP1A1/1B1/EH, CYP peroxidase, and AKR pathways which
leads to produce reactive DNA adducts, results in DNA mutations and change in the
downstream gene expression profile, ultimately leads to the development of cancer.
Mutations in xenobiotic metabolic enzymes, tumor suppressor genes (e.g. p53) and
genes responsible for cancer susceptibility from various age groups, ethnicities, and
gender [40].
Endocrine and Endocrine Disruptors
In the regulation of fats, carbohydrates, and proteins metabolism, endocrine system
plays a crucial role to provide fuel to the body in the form of energy, all the times.
When the availability is more, endocrine hormones are accountable to mobilize and
store excess energy in the form of fats in various parts of the body. During scarcity
or unavailability of energy sources, this stored energy is mobilized again to compensate need of the body and most importantly to maintain constant blood glucose
level. An imbalance between these two processes occurs whenever there is change
in hormones secretion or production to drive the processes of metabolism.
A. Khan et al.