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Additionally, living in high-altitude anoxic environments triggers physiological adaptations including hypoxia-induced modulation of CYP450 enzymes, altering drug metabolism rates ( 3.2.3 Lifestyle exposures 3.2.3.1 Tobacco smoke It is known that cigarette smoking significantly induces CYP1A2 activity, with heavy smokers (20 cigarettes per day) showing almost a two-fold increase in its activity compared to nonsmokers

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Mechanistically, oxidative stress activates p16-pRb effector pathway which is thought to play a vital role in SIPS mediation 11