Certain particle compounds may directly generate ROS in vivo because of their surface chemistry (eg, metals, organic compounds, and semiquinones) or after bioactivation by cytochrome P450 systems (eg, polycyclic aromatic hydrocarbon conversion to quinones).6, 290 a, 290 b A particle surface or anions present on otherwise more inert particles may disrupt iron homeostasis in the lung and thereby also generate ROS via Fenton reactions.291 Other PM constituents may do so indirectly by the upregulation of
endogenous cellular sources (eg, nicotinamide adenine dinucleotide phosphate [NADPH]-RRB- oxidase) 292,293 or by perturbing organelle function (eg, mitochondria) by taken - up PM components.261 Particle stimulation of irritant and afferent ANS fibers may also play a role in local and systemic oxidative stress formation.294 Given the rich antioxidant defenses in the lung fluid, secondarily generated oxidization products of
endogenous molecules (eg, oxidized phospholipids,
proteins) or a reduction in
endogenous antioxidants per se may be responsible at least in part for the state of oxidative stress in the lungs (along with instigating the subsequent
cellular responses) rather than ROS derived directly from PM and its constituents.
An anti-cancer diet also needs to be low or moderate in complete
protein and high - insulemic index foods (to reduce growth promoting IGF - 1), and perhaps low in methionine specifically while high in fiber, phytochemical hormetics (to induce
endogenous antioxidant responses and toxin removal), epigenetically active compunds (to reexpress tumor suppressor genes for induce
cellular senescence or apoptosis), inflammation inhibitors, and antiangiogenetic compounds.