An Assessment on Ethanol-Blended Gasoline/Diesel Fuels on Cancer Risk and Mortality

Abstract

Although cancer is traditionally considered a genetic disease, the epigenetic abnormalities, including DNA hypermethylation, histone deacetylation, and/or microRNA dysregulation, have been demonstrated as a hallmark of cancer. Compared with gene mutations, aberrant epigenetic changes occur more frequently, and cellular epigenome is more susceptible to change by environmental factors. Excess cancer risks are positively associated with exposure to occupational and environmental chemical carcinogens, including those from gasoline combustion exhausted in vehicles. Of note, previous studies proposed particulate matter index (PMI) as a measure for gasoline sooting tendency, and showed that, compared with the other molecules in gasoline, 1,2,4-Trimethylbenzene, 2-methylnaphthalene and toluene significantly contribute to PMI of the gasoline blends. Mechanistically, both epigenome and genome are important in carcinogenicity, and the genotoxicity of chemical agents has been thoroughly studied. However, less effort has been put into studying the epigenotoxicity. Moreover, as the blending of ethanol into gasoline substitutes for carcinogens, like benzene, toluene, xylene, butadiene, and polycyclic aromatic hydrocarbons, etc., a reduction of secondary aromatics has been achieved in the atmosphere. This may lead to diminished cancer initiation and progression through altered cellular epigenetic landscape. The present review summarizes the most important findings in the literature on the association between exposures to carcinogens from gasoline combustion, cancer epigenetics and the potential epigenetic impacts of biofuels.

Keywords: BTEX; BTX; COVID-19; DNA methylation; DNA methyltransferases; DNMT; HAT; HDAC; PAHs; PM emission; TET; benzene; biofuels; carcinogens; epigenotoxicity; ethanol; gasoline combustion; genotoxicity; histone acetyltransferases; histone deacetylases; histone modification; microRNAs; ten–eleven translocation methylcytosine dioxygenases.

Figure 1

Crosstalk among epigenetic regulators determines cancer cell fate. Left: HDACs, DNMTs and TETs cooperatively regulate DNA methylation and his-tone modification change target expression; Right: HDACs, DNMTs, TETs and unknown factors form complex binding target promoters controlling their levels; * microRNA deregulation feedback to inhibit epigenetic regulators.?, unknown factor; ↑ upregulation; ↓ downregulation; ┤ Inhibition.

Figure 2

Air pollutants may induce malignant transformation via epigenetic aberrations. Chemicals from gasoline exhausts enter the human cells and modulate epigenetics through multiple mechanisms (e.g., abnormal levels of SAM and cytokine; unknown pathways), leading to malignant transformation. In human cells, left: HDACs, DNMTs and TETs cooperatively regulate DNA methylation and histone modification, thus changing target expression; right: HDACs, DNMTs, TETs and unknown factors (?) form complex binding target promoters, determining their levels; * microRNA deregulation feeds back to negatively modulate the expression of all epigenetic regulators.