Smoking increases human nasal epithelial cytochrome P450 1A1 gene transcription.
Brundage-R; Rossignol-T; Hanshaw-R; Lucas-M; Fekedulegn-D; Opheim-G; Kashon-M; Castranova-V; Weissman-D
Toxicologist 2003 Mar; 72(S-1):110
Respiratory tract carcinogenesis, mediated by polycyclic aromatic hydrocarbons (PAH) such as those associated with cigarette smoke, is in part due to induction of cytochrome P450 1A1 (CYP1A1) mRNA and protein expression with subsequent carcinogenic activation of PAH by CYP1A1. Respiratory epithelium is a key target tissue for these events. We therefore hypothesized that CYP1A1 mRNA expression level could be noninvasively monitored in human nasal epithelium, the most easily sampled respiratory epithelium, as a potentially pre-carcinogenic health effect of exposures to inhalants such as cigarette smoke. Subjects were healthy office and garage workers. Demographic, smoking, and occupational histories were obtained by questionnaire. Nasal epithelium was collected using Rhinoprobes(Tm) to obtain scrapings from subjects inferior turbinates. Tissue samples were stabilized using RNLater(Tm) to inhibit RNAses. RNA was extracted using Trizol(Tm). Isolated RNA was reverse transcribed, and abundance of mRNA encoding CYP1A1, IL-8, and G3PDH was evaluated by real time TaqMan(Tm)PCR. Cycle threshold (CT) was used as a measure of the mRNA level in each sample, standardized between samples by using the CT for G3PDH, and the following equation used to calculate a delta CT: CT (CYP1A1 or IL-8) minus CT (G3PDH) = delta CT. Data demonstrated a significant increase (p < 0.001) of CYP1A1 expression in current smokers (n=16) as compared to non-smokers (n=17) or former smokers (n=23) in our study group. No significant differences were seen in IL-8 expression levels between these groups nor were any associations apparent between occupational exposures and expression levels of CYP1A1 or IL-8. We conclude that CYP1A1 gene expression can be monitored noninvasively in human nasal epithelium, and that expression level can be modulated by exposures to agents such as cigarette smoke.
Smoke-inhalation; Smoking; Genes; Carcinogenesis; Hydrocarbons; Cigarette-smoking; Health-hazards; Inhalation-studies; Exposure-levels; Workers; Workplace-studies; Demographic-characteristics; Occupational-exposure; Sampling
The Toxicologist. Society of Toxicology 42nd Annual Meeting and ToxExpo, Cutting-Edge Science, Networking, New Perspectives, March 9-13, 2003, Salt Lake City, Utah