Avaliação dos efeitos da exposição aos BTEX (benzeno, tolueno, etilbenzeno e xilenos) no genoma dos trabalhadores de postos de combustíveis

Abstract

BTEX (benzene, toluene, ethylbenzene and xylenes) are aromatic compounds used as fuel solvents, which are known to be toxic and carcinogenic. Gas station workers (GSWs) are chronically exposed to these chemicals, which are volatiles and solubles. The individual susceptibility of GSWs and the early effects of this exposure are discussed in three papers, summarized as follows: Article 1. The frequency of chromosome alterations (CAs) of peripheral blood lymphocytes is considered a biomarker of early effect, being important in the prevention of occupational oncologic diseases. We evaluated 60 GSWs through the FISH technique, applying it to chromosomes 1, 2, and 4; in addition, blood exams and medical and socio-demographic evaluation were performed. We found a young population (median: 36 years) but with a long period of exposure time (median 16 years) and a high population frequency of CAs (9.3 / 1000 metaphases). Of the workers 16.6% (10/60) had a high number of CAs (> 10 CAs per 1000 metaphases), and translocations were the most common CAs (43.6%). Statistical analysis revealed a significant difference in skin color (P = 0.002). Therefore, more studies are needed to better characterize the damage associated with the genome of these workers. Article 2. We report the cases of two women with symptoms of BTEX intoxication and abortions reports. In both cases, complex chromosome rearrangements (CCRs) were identified applying the FISH technique (case 1- 46,XX, der(1) t(1;4) ,der(4)t(1;4;?),ace(1),ace(1); case 2 -der(4)ins(2;4)). A rare type of NK cells (NKbright) was also found in the peripheral blood of these workers. Thus, this was the first study to suggest a possible causal relationship between depletion of the NK cell cytotoxicity function, first trimester miscarriage, and CCRs. Article 3. Case-control study in which 114 workers and 115 controls were evaluated, using two types of biomarkers: one with an early effect (CAs through FISH technique) and the other with susceptibility (genotyping of RAD51/G135C, ATM/P1054R, and CHEK2/T470C polymorphisms). Medical and sociodemographic evaluation was also applied. A high frequency of ACs (9.8 CAs / 1,000) was observed. Of the workers 19.1% had a high number of CAs. Also, a high number of women (p = 0.035) and lower monocyte levels in blood exams (P = 0.024), as well as untrust in automatic fuel supply (P = 0.027) were observed in the group with the highest number of CAs (group 2). The presence of RAD51 / G135C polymorphism was associated with GSWs when compared to the controls (P = 0.011), and to the number of CAs per worker (P = 0.008). The specificity of RAD51/G135C to detect workers with CAs was 87%, while that of ATM/ P1054R was 79%. No allele variant was found for CHEK2 / T470C. Thus, the RAD51 / G135C polymorphism is promising marker of susceptibility to the development of cancer to apply in GSW monitoring.