Carcinogenic potential and genomic instability of beryllium sulphate in BALB/c-3T3 cells

  • Nagalakshmi Keshava
  • Gu Zhou
  • Michelle Spruill
  • Mang Ensell
  • Tong-man Ong
Part of the Developments in Molecular and Cellular Biochemistry book series (DMCB, volume 34)


Occupational exposure to beryllium (Be) and Be compounds occurs in a wide range of industrial processes. A large number of workers are potentially exposed to this metal during manufacturing and processing, so there is a concern regarding the potential carcinogenic hazard of Be. Studies were performed to determine the carcinogenic potential of beryllium sulfate (BeSO4) in cultured mammalian cells. BALBIc-3T3 cells were treated with varying concentrations of BeSO4for 72 h and the transformation frequency was determined after 4 weeks of culturing. Concentrations from 50-200 jtg BeSO4/m1, caused a concentration-dependent increase (9-41 fold) in transformation frequency. Non-transformed BALB/c-3T3 cells and cells from transformed foci induced by Be5O4were injected into both axillary regions of nude mice. All ten Be-induced transformed cell lines injected into nude mice produced fibrosarcomas within 50 days after cell injection. No tumors were found in nude mice receiving non-transformed BALE/c-3T3 cells 90 days post-injection. Gene amplification was investigated inK-ras,c-myc,c-fos,c jun,c-sis,erb-B2andp53using differential PCR while random amplified polymorphic DNA fingerprinting was employed to detect genomic instability. Gene amplification was found inK-rasandc jun, however no change in gene expression or protein level was observed in any of the genes by Western blotting. Five of the 10 transformed cell lines showed genetic instability using different random primers. In conclusion, these results indicate that BeSO4is capable of inducing morphological cell transformation in mammalian cells and that transformed cells induced by BeSO4are potentially tumorigenic. Also, cell transformation induced by BeSO4may be attributed, in part, to the gene amplification ofK-rasandc-junand some BeSO4-induced transformed cells possess neoplastic potential resulting from genomic instability. (Mol Cell Biochem222:69-76, 2001)

Key words

cell transformation tumorigenicity genomic instability  beryllium sulphate 


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Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Nagalakshmi Keshava
    • 1
  • Gu Zhou
    • 1
  • Michelle Spruill
    • 1
  • Mang Ensell
    • 1
  • Tong-man Ong
    • 1
  1. 1.Health Effects Laboratory DivisionNational Institute for Occupational Safety and Health, Centers for Disease Control and PreventionMorgantownUSA

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