G. Angeli

Urinary excretion of mutagens, thioethers and d-glucaric acid in workers exposed to bitumen fumes

SummaryThe authors carried out biological monitoring of the mutagenic/carcinogenic hazards associated with exposure to bitumen fumes during paving operations, analysing some biological parameters in the urine of a group of exposed workers. The urine samples were studied for mutagenicity by the Ames test and for thioethers concentration. d-Glucaric acid urine excretion was also determined to investigate the enzymatic induction potential of bitumens. Even though, in a previous environmental monitoring phase, a low content of mutagenic/carcinogenic compounds was found in bitumen and air samples, urinary mutagenicity data of exposed workers were statistically higher than those of a group of unexposed subjects. The urinary mutagenicity increased further if exposure to bitumens was associated with cigarette smoking. Thioethers were higher only in subjects exposed simultaneously to bitumens and cigarettes. d-Glucaric acid excretion did not increase significantly. The authors think that this type of coupled environmental and biological monitoring is a valid tool for a better evaluation of the mutagenic/carcinogenic exposure to bitumens or similar complex mixtures.

Mutagenicity studies and D-glucaric acid determination in urine of workers exposed to mineral oils

SummaryUrine from workers of a cold-rolling steel plant exposed to mineral oils were tested for the mutagenic activity by the Salmonella/microsome assay, and for D-glucaric acid content as a measure of hepatic mixed-function oxidase activity. An occupationally unexposed group served as control. The biological monitoring phase followed an environmental phase carried out in the working environment that showed a substantially low mutagenic/carcinogenic risk for the exposed workers. Urine samples were collected before, during and after work. From the results it was observed that the urinary mutagenicity was detectable only with TA98 strain in the presence of enzymatic activation (+ S9 mix). Further addition of beta-glucuronidase did not give any enhanced mutagenic effects. There was a significant difference in urinary mutagenicity between the exposed and control workers. However, in both groups the highest mutagenicity data was found in smokers: both exposed smoking workers and smoking controls had significantly higher urine mutagenicity than the non-smoking exposed and control workers. The results suggested a synergistic effect of smoking with exposure to mineral oils: the mutagenicity of urine from exposed smokers was significantly higher than that of control smokers. There was no difference in urinary D-glucaric acid results between exposed and unexposed groups, however, smokers of both groups had a significant increase in D-glucaric acid excretion. The authors suggest that even for this workplace with its low mutagenic/carcinogenic risk, smoking could interact with the complex mixtures present in the environment, and thus modify urinary mutagenicity data.

Chemical composition and genotoxic activity of petroleum derivatives collected in two working environments

Pitch and bitumen, two complex petroleum derivative mixtures, were studied for both their chemical composition and their mutagenic/DNA damaging activity. While bitumen revealed no genotoxic effect and low polycyclic aromatic hydrocarbons (PAHs) concentration, petroleum pitch showed a high concentration of mutagenic/carcinogenic PAHs, and also an elevated mutagenic activity when assayed by the Ames test, in the presence of postmitochondrial rat liver fractions. The in vitro mutagenic activity was detectable as frameshift mutation by assaying the pitch both as an in toto mixture and after HPLC fractionation, the most polar fractions being the most active. In contrast, both derivatives showed no in vivo DNA damage in rat liver, using the DNA alkaline elution technique and the fluorometric assay of DNA unwinding.

Enzyme induction in rat lung and liver by condensates and fractions from main-stream and side-stream cigarette smoke

Aryl hydrocarbon hydroxylase (AHH) and dimethylnitrosamine demethylase (DMND) activities in pulmonary and hepatic tissues of male Sprague-Dawley rats were assayed following pretreatment with known inducers (benzo[a]pyrene, 3-methylcholanthrene, Aroclor 1254, phenobarbital) and with main-stream (MS) and side-stream (SS) cigarette smoke condensates and their related fractions. Biochemical assays by spectrophotofluorimetry (AHH activity) and spectrophotometry (DMND activity) and by a biological assay (Ames test) were performed to detect AHH and DMND induction. Ames test proved to be much less sensitive than the spectrophotofluorimetric analysis for AHH determination. Both main-stream and side-stream cigarette smoke condensates and some fractions, containing water-soluble bases, water-insoluble bases, and polycyclic aromatic hydrocarbons, were found to induce AHH activity in lung and liver, the lung being induced to the greatest extent. The highest levels of AHH inducibility were found for the SS-smoke condensate and related fractions. In particular, the insoluble bases fractions gave the highest induction. On the contrary, pulmonary DMND activity was not affected by pretreatment with the same materials, while hepatic DMND response was only minimally induced by Aroclor and phenobarbital treatment.

Enzymatic activities of human lung tissue: relationship with smoking habits

Twenty-two S12 preparations of surgical lung specimens obtained from smoker and non-smoker cancer patients were assayed to detect aryl hydrocarbon hydroxylase (AHH), dimethylnitrosamine demethylase (DMND), and glutathione-S-transferase (GST) activities, in both normal and neoplastic lung tissue from the same patients. Pulmonary fractions were also tested for their ability to activate some precarcinogens into mutagenic metabolites in the Ames test. Statistically significant differences were found for AHH and DMND activities between normal and neoplastic tissue of smoker patients. In addition, higher AHH activity in the neoplastic tissue of the smoker group was observed compared with that found in the non-smoker group. No differences were found for GST activity. All the lung S12 preparations were able to metabolize water-soluble bases and water-insoluble bases, derived from main-stream cigarette smoke condensate, into mutagenic agents in the Salmonella test system. However, S12 preparations from smoker group neoplastic tissues were more effective.