Mutagenic activity of overnight urine from healthy non‐smoking subjects

Abstract

Urinary mutagenicity was evaluated in relation to environmental mutagen exposure (i.e., diet, indoor/outdoor activities, residential area etc.) on the day prior to sample collection, and also considering factors that contribute to the variability of Salmonella mutagenicity assay results. Overnight urine samples from 283 healthy non-smoking residents of northeast Italy (46% males, 20-62 years) were analyzed for mutagenicity on sensitive Salmonella typhimurium strain YG1024 with S9 mix employing the preincubation version of the plate incorporation assay (i.e., the Salmonella reverse mutation test). Urinary mutagenicity varied between 0.02 and 9.84 rev/ equiv. ml, and 7% of samples were positive (i.e., sample elicited a two-fold increase in revertants). There was an evident increase in mutagenicity in subjects with increased intake of mutagen-rich meals (n = 80) (P < 0.01 and positive urine 13% vs. 5%, P = 0.025). Indoor-exposed subjects (n = 65) also showed a higher percentage of positive urine (14% vs. 5%, P = 0.015). In particular, those subjects exposed to cooking fumes the previous evening (n = 28) revealed higher urinary mutagenicity (P = 0.035, positive urine 25% vs. 5%, P < 0.001) than non-indoor exposed. The sources of variability of the mutagenicity assay, mainly the histidine content of the urine concentrate (z = 4.06, P < 0.0001), and to a lesser extent bacterial inoculum size (z = 2.33, P = 0.019), also significantly influenced urinary mutagenicity values. In a linear multiple regression analysis, their effects were still significant (i.e., histidine content P = 0.026 and inoculum size P = 0.021), but the effects of diet, indoor exposure, and other environmental exposures (i.e., traffic and heating system exhausts, residential area) were not. It is concluded that the previous day's exposure to mutagen-rich meals and cooking fumes may influence the presence of mutagenic activity in the overnight urine of non-smoking subjects. This mutagenic activity, which remains in contact with bladder mucosa for several hours, could be considered risk factors for colorectal adenoma and possibly other cancers (i.e., bladder) in non-smokers. Accurate control of histidine content and bacterial inoculum size is strongly recommended when investigating the mutagenic activity of urine from non-smokers.

Global and gene‐specific promoter methylation changes are related to anti‐B[a]PDE‐DNA adduct levels and influence micronuclei levels in polycyclic aromatic hydrocarbon‐exposed individuals

“…All subjects were noncurrent smokers, defined as former smokers who had stopped smoking at least one year before sample collection or those who had never smoked. Urine analysis of nicotine and its metabolites 29 confirmed that all subjects were nonexposed to tobacco smoke as they had urine nicotine concentrations <0.01 mg/mmol creatinine.…”

Ultrasensitive High-Resolution Mass Spectrometric Analysis of a DNA Adduct of the Carcinogen Benzo[a]pyrene in Human Lung

“…42 Pavanello et al used HPLCfluorescence to analyze BaP-tetraol released from DNA of lymphomonocytes and reported their presence in 248 out of 585 subjects at a mean level of 1.28 ± 2.80 adducts per 10 8 nucleotides. 43 Mensing et al also reported BaP-tetraol released from white blood cells as determined by HPLC-fluorescence with levels in the range of 1−2 adducts per 10 8 nucleotides. 44 These contrasting results between studies using mass spectrometric techniques versus those using HPLC-fluorescence to analyze BaP-tetraols released from DNA upon acid hydrolysis are difficult to reconcile.…”

Effects of Switching to the Tobacco Heating System 2.2 Menthol, Smoking Abstinence, or Continued Cigarette Smoking on Biomarkers of Exposure: A Randomized, Controlled, Open-Label, Multicenter Study in Sequential Confinement and Ambulatory Settings (Part 1)

“… 30 The source of the high variability of the urine mutagenicity values is likely due to (1) the relative high sensitivity of this assay to diet, as previously reported, 31 even in nonsmokers, (2) individual metabolic differences, and (3) variability of the cellular-based assay itself. 32 …”