The dose-response relationship of the benzene covalent interaction with biological macromolecules from rat organs was studied. The administered dose range was 3.6 x 10(7) starting from the highest dosage employed, 486 mg/kg, which is oncogenic for rodents, and included low and very low dosages. The present study was initially performed with tritium-labeled benzene, administered by IP injection. In order to exclude the possibility that part of the detected radioactivity was due to tritium incorporated into DNA from metabolic processes, 14C-benzene was then also used following a similar experimental design. By HPLC analysis, a single adduct from benzene-treated DNA was detected; adduct identification will be attempted in the near future. Linear dose-response relationship was observed within most of the range of explored doses. Linearity was particularly evident within low and very low dosages. Saturation of benzene metabolism did occur at the highest dosages for most of the assayed macromolecules and organs, especially in rat liver. This finding could be considered as indicative of the dose-response relationship of tumor induction and could be used in risk assessment.
Reducing children’s exposure to air pollutants should be considered a primary goal, especially for the most vulnerable subjects. The goal of this study was to test the effectiveness of applying a protocol in the event of alert days, i.e., days with forecasted PM10 levels above the EU limit value (50 µg/m3). The test was conducted, before the onset of SARS-CoV-2 restrictions, in a classroom of a primary school in Parma (Italy)—a highly polluted area in Northern Italy. The protocol included indications for the frequency of opening windows and doors, as well as the activation of an air purifier. Teachers and students were asked to apply the protocol only in the event of alert days, while no indications were provided for non-alert days. A monitoring system measuring PM1, PM2.5, PM10, CO2, and NO2 was deployed in the classroom. Measurements of the same parameters were also performed outdoors near the school. The application of the protocol reduced the indoor/outdoor (I/O) ratio for all toxic pollutants. The reduction was also remarkable for PM10—the most critical air quality parameter in the study area (1.5 and 1.1 for non-alert and alert days, respectively). Indoor concentrations of PM10—especially during non-alert days—were often higher than outdoors, showing a major contribution from resuspension due to the movement of people and personal cloud. The protocol did not cause any increase in indoor CO2 levels. Our findings showed that the application of a ventilation protocol together with the contribution of an air purifier may represent an effective way to reduce children’s exposure to air pollution during severe air pollution episodes. Considering the onset of COVID-19 and the airborne transmission of pathogens, this protocol now has more meaningful implications for children’s welfare, and can be integrated with protocols designed as measures against the spread of SARS-CoV-2.
Twenty-two hours after i.p. injection to male Wistar rats and BALB/c mice para-dichlorobenzene (p-DCB) is bound covalently to DNA from liver, kidney, lung and stomach of mice but not of rats. DNA adducts in mouse liver are repaired in seventy-two hours. The covalent binding index value, calculated on the labelling of mouse liver DNA, classifies p-DCB as a weak initiator with an oncogenic activity lower than that of chlorobenzene. The labelling of RNA and proteins from the different organs of both species is, however, low. In vitro interaction with calf thymus DNA mediated by mouse and rat microsomes from liver and lung did occur. Binding extent was strongly reduced by addition of 2-diethylaminoethyl-2,2-diphenylvalerate hydrochloride (SKF 525-A) to the microsomal standard incubation mixture, whereas it was enhanced by adding GSH. Cytosolic fractions from kidney and lung were able to induce binding of p-DCB to DNA to a lower extent with respect to microsome-mediated binding. These results indicate that microsomal mixed function oxidase system and microsomal GSH-transferases can be involved in overall activating metabolism whereas cytosolic GSH-transferases play a minor role. This study, which is a part of a structure-activity relationship approach on benzene and its haloderivatives, provides the first evidence of genotoxicity of p-DCB in mammalian cell. It allows to partly explain variations of susceptibility of different species to hepatocarcinogenesis and of hepatotoxicity of different isomers.
Chloroform was bound covalently to DNA, RNA and proteins of rat and mouse organs in vivo after i.p. injection. Covalent Binding Index values of rat and mouse liver DNA classify chloroform as a weak initiator. Labelings of RNA and proteins from various organs of both species were higher than that of DNA. In an in vitro cell-free system, chloroform was bioactivated by cytochrome P450-dependent microsomal fractions, by cytosolic GSH-transferases from rat and mouse liver, and particularly by the latter enzymes from mouse lung. This observation suggests that GSH plays a role in the binding of chloroform metabolites to DNA. The presence of both microsomal and cytosolic enzymatic systems in the standard incubation mixture generally led to an additive or synergistic bioactivating effect for rat and mouse, respectively.
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