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Cellular alterations and modulation of protein expression in bitumen-challenged human osteoblast cells

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Abstract

Purpose

There are many arguments on the carcinogenic potential of bitumen extract. The mechanism of bitumen-induced damage is not well understood at the molecular level. Therefore, in the present study, cell-transforming and tumor-inducing potential of bitumen extract was studied using in vitro [human osteosarcoma (HOS) cells] and in vivo [nude and severe combined immunodeficiency (SCID) mice] models.

Methods

Gas chromatography/mass spectrometry (GC/MS) analysis was carried out to find out the existence of carcinogenic compounds in the bitumen extract. Cell transformation test, anchorage independence assay, karyotyping assay, tumorigenicity assay, and 2-DE analysis were used to find out the effect of bitumen using the in vitro and in vivo models.

Results

GC/MS analysis showed the existence of carcinogenic compounds in the bitumen extract. HOS cells were treated with different concentrations (25, 50, and 100 μl/ml) of bitumen extract. Compared to the parental HOS cells, bitumen transformants (HOS T1 and HOS T2) showed the characteristics of anchorage independency, chromosomal anomaly, and cellular transformation. Interestingly, bitumen transformants were not able to form tumor in nude/SCID mice. Proteomic analysis revealed the existence of 19 differentially expressed proteins involved in progression of cancer, angiogenesis, cell adhesion, etc.

Conclusions

Exposure of bitumen extract to HOS cells results in the cellular transformation similar to cancer cells and can modulate proteins involved in the progression of cancer. We state that the non-tumorogenic potential of bitumen transformant in nude/SCID mice can be attributed to the downregulation of galectin-1, chromodomain helicase DNA-binding protein 1-like gene, and membrane-associated guanylate kinase 2 protein.

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Acknowledgments

The authors are thankful to the Council of Scientific and Industrial Development (C.S.I.R.) for providing the funds through CSIR Network Project and to Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Khargar, Navi Mumbai, India for providing the necessary help.

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Authors and Affiliations

  1. National Environmental Engineering Research Institute, Nehru Marg, Nagpur, India

    Alka Dhondge, Subin Surendran, Muhil Vannan Seralathan, Pravin K. Naoghare, Kannan Krishnamurthi, Sivanesan Saravana Devi & Tapan Chakrabarti

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  1. Alka Dhondge
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  2. Subin Surendran
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  3. Muhil Vannan Seralathan
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  4. Pravin K. Naoghare
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  7. Tapan Chakrabarti
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Correspondence to Sivanesan Saravana Devi.

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Dhondge, A., Surendran, S., Seralathan, M.V. et al. Cellular alterations and modulation of protein expression in bitumen-challenged human osteoblast cells. Environ Sci Pollut Res 19, 4030–4041 (2012). https://doi.org/10.1007/s11356-012-0879-z

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  • DOI: https://doi.org/10.1007/s11356-012-0879-z

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