Modulation of CYP1A1/CYP1A2 levels markedly reduced parent drug concentrations, significantly altering metabolite pharmacokinetics (PK) in humanized mice <i>in vivo</i><b>Conclusions:</b> We demonstrate that a P450 enzyme expressed in smokers' lungs and lung tumors has the capacity to metabolise osimertinib.
In adjacent histologically normal lung from lung cancer patients (n = 120), low levels of DNA methylation of the CYP1A1 enhancer were related to high levels of smoking-induced hydrophobic DNA adduct (p < 0.03), and to the presence of TP53 or K-ras mutations in the corresponding lung tumors (p < 0.03).
CYP1A1 polymorphisms and risk of lung cancer in non-smoking Chinese women: influence of environmental tobacco smoke exposure and GSTM1/T1 genetic variation.
Previous studies from this and other laboratories have shown that treatment of pregnant mice with 3-methylcholanthrene (MC) caused lung tumors in the offspring, the incidence of which correlated with fetal inducibility of Cyp1a1.
In patients with inducible CYP1A1, the expressing GSTM1 gene appeared to have a protective effect against contracting bronchial lung cancer, since 88% (14/16) of the lung tumours in this patient group were peripheral, whereas almost equal numbers of peripheral and bronchial tumours were observed in those patients lacking the gene (P = 0.037).