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Differential toxic effects of methyl tertiary butyl ether and tert-butanol on rat fibroblasts in vitro

Institute of General Pathology, "Giovanni XXIII" Cancer Research Center, Catholic University of Sacred Heart, Rome, Italy; Laboratory of Molecular Oncology, Centro di Riferimento Oncologico Regionale della Basilicata (CROB), Istituto di Ricovero e Cura a Carattere Scientifico, Rionero in Vulture, Potenza

I Iavicoli

Institute of Occupational Medicine, Catholic University of Sacred Heart, Rome, Italy Iavicoli.ivo{at}rm.unicatt.it

B De Paola

Institute of General Pathology, "Giovanni XXIII" Cancer Research Center, Catholic University of Sacred Heart, Rome, Italy

G Bianchino

Institute of General Pathology, "Giovanni XXIII" Cancer Research Center, Catholic University of Sacred Heart, Rome, Italy; Laboratory of Molecular Oncology, Centro di Riferimento Oncologico Regionale della Basilicata (CROB), Istituto di Ricovero e Cura a Carattere Scientifico, Rionero in Vulture, Potenza

A Boninsegna

Institute of General Pathology, "Giovanni XXIII" Cancer Research Center, Catholic University of Sacred Heart, Rome, Italy

A Bergamaschi

Institute of Occupational Medicine, Catholic University of Sacred Heart, Rome, Italy

A Pietroiusti

Department of Biopathology/Occupational Medicine, Tor Vergata University, Rome, Italy

A Cittadini

Institute of General Pathology, "Giovanni XXIII" Cancer Research Center, Catholic University of Sacred Heart, Rome, Italy; Laboratory of Molecular Oncology, Centro di Riferimento Oncologico Regionale della Basilicata (CROB), Istituto di Ricovero e Cura a Carattere Scientifico, Rionero in Vulture, Potenza

Methyl tertiary butyl ether (MTBE) is the most widely used motor vehicle fuel oxygenate since it reduces harmful emissions due to gasoline combustion. However, the significant increase in its use in recent years has raised new questions related to its potential toxicity. In fact, although available data are somehow conflicting, there is evidence that MTBE is a toxic substance that may have harmful effects on both animals and humans and an unresolved problem is the role played by MTBE metabolites, especially tertiary butyl alcohol (TBA), in determining toxic effects due to MTBE exposure. In this study, the toxic effects of MTBE have been analyzed on a normal diploid rat fibroblast cell line (Rat-1) and compared to the effects of TBA. The results obtained suggest that both MTBE and TBA inhibit cell growth in vitro but with different mechanisms in terms of effects on the cell cycle progression and on the modulation of cell cycle regulatory proteins. In fact, MTBE caused an accumulation of cells in the S-phase of the cell cycle, whereas TBA caused an accumulation in the G0/G1-phase with different effects on the expression of cyclin D1, p27Kip1, and p53. Moreover, both MTBE and TBA were also shown to induce DNA damage, as assessed in terms of oxidative DNA damage and nuclear DNA fragmentation, that appeared to be susceptible of repair by the cell DNA-repair machinery. In conclusion, these findings suggest that both MTBE and TBA can exert, by acting through different molecular mechanisms, important biological effects on fibroblasts in vitro. Further studies are warranted to shed light on the mechanisms responsible for the observed effects and on their potential significance for the in-vivo exposure.

Key Words: fuel oxygenates • oxidative damage • pollution • rat fibroblasts • toxicity

Toxicology and Industrial Health, Vol. 25, No. 2, 141-151 (2009)
DOI: 10.1177/0748233709104867


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