Effects of cigarette smoking and exposure to cadmium and lead on phenotypic variability of hepatic CYP2A6 and renal function biomarkers in men

Metals in cigarette smoke

“…Mortada et al (11) reported that the mean whole blood Cd content in smokers was 1.9 times higher that in non-smokers (2.67 + 1.21 mg/l and 1.37 + 0.45 mg/l respectively (mean + SD), average age 30 years). Satarug et al (12) reported that smokers have a 1.7 fold increase of serum Cd content compared to non-smokers (0.92 + 0.83 mg/l and 0.55 + 0.48 mg/l, average age 36 years). Barany et al (13) reported that serum Cd values of young smokers was at least 3.1 fold increased in comparison to young non-smokers (0.61 + 0.75 mg/l and below the lower limit of detection (LOD) 0.2 mg/l; average age 16 years).…”

“…Mortada et al (11) report blood Pb levels (mean + SD) in non-smokers of 101.6 + 30.9 mg/l and in smokers of 143.7 + 33.8, whereas Satarug et al (12) report Pb serum levels of 4.2 + 5.4 mg/l in non-smokers and 9.0 + 12 in smokers. The dramatic difference between blood and serum Pb concentrations is due to the fact that Pb in the circulation is mainly bound to erythrocytes (14).…”

“…A number of studies have shown that this accumulation of Cd in kidneys causes tubular dysfunction and renal end stage failure, but there is also evidence that the amount of cadmium delivered by smoking is to small to cause kidney failure (11,12,14). Further, Cd has been shown to reduce bone mineral density (osteoporosis) and to cause osteomalacia, the combination of which is called itai itai (ouch-ouch) disease (9,14).…”

Smoking

“…According to studies from Egypt, smoking has toxic effects on tubular cells, which are synergistic to occupational Pb (56), mercury (57), and silica (58) exposure. Dietary Cd and Pb seems to confer mild tubular dysfunction, whereas dietary exposure plus cigarette smoking is associated with tubular plus glomerular dysfunction (59). The dietary risk for renal Cd toxicity in the general population of the United States (60) and Japan (61) seems to be negligible, provided that no additional exposures from other sources are present.…”

Mechanism-Based Inactivation of Cytochrome P450 2A6 by Decursinol Angelate Isolated fromAngelica Gigas

“…CYP2A6 is one of the forms of P450 expressed in the human respiratory tract (Smith et al, 1995;Macé et al, 1998), which is responsible for the metabolic activation of tobaccospecific nitrosamines, including 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (Tiano et al, 1994;Smith et al, 1995), a potent pulmonary-specific carcinogen (Hecht, 1998), to yield genotoxic metabolites. The expression of CYP2A6 is controlled by environmental and/or genetic factors (Oscarson, 2001;Paschke et al, 2001;Satarug et al, 2004). An individual's adverse response to exposure to CYP2A6 substrates, such as smoking, may depend on the level of CYP2A6 present in that individual.…”