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

Keshava, N Zhou, G Spruill, M Ensell, M Ong, TM

N. Keshava et al., Carcinogenic potential and genomic instability of beryllium sulphate in BALB/c-3T3 cells, MOL C BIOCH, 222(1-2), 2001, pp. 69-76

31

INGLESE

Article

Cell & Developmental Biology

MOLECULAR AND CELLULAR BIOCHEMISTRY

0300-8177 → ACNP

222

1-2

2001

69 - 76

ISI

0300-8177(200106)222:1-2<69:CPAGIO>2.0.ZU;2-P

Occupational exposure to beryllium (Be) and Be compounds occurs in a wide r ange of industrial processes. A large number of workers are potentially exp osed to this metal during manufacturing and processing, so there is a conce rn regarding the potential carcinogenic hazard of Be. Studies were performe d to determine the carcinogenic potential of beryllium sulfate (BeSO4) in c ultured mammalian cells. BALB/c-3T3 cells were treated with varying concent rations of BeSO4 for 72 h and the transformation frequency was determined a fter 4 weeks of culturing. Concentrations from 50-200 mug BeSO4/ml, caused a concentration-dependent increase (9-41 fold) in transformation frequency. Non-transformed BALB/c-3T3 cells and cells from transformed foci induced b y BeSO4 were injected into both axillary regions of nude mice. All ten Be-i nduced transformed cell lines injected into nude mice produced fibrosarcoma s within 50 days after cell injection. No tumors were found in nude mice re ceiving non-transformed BALB/c-3T3 cells 90 days post-injection. Gene ampli fication was investigated in K-ras, c-myc, c-fos, c-jun, c-sis, erb-B2 and p53 using differential PCR while random amplified polymorphic DNA fingerpri nting was employed to detect genomic instability. Gene amplification was fo und in K-ras and c-jun, however no change in gene expression or protein lev el was observed in any of the genes by Western blotting. Five of the 10 tra nsformed cell lines showed genetic instability using different random prime rs. In conclusion, these results indicate that BeSO4 is capable of inducing morphological cell transformation in mammalian cells and that transformed cells induced by BeSO4 are potentially tumorigenic. Also, cell transformati on induced by BeSO4 may be attributed, in part, to the gene amplification o f K-ras and c-jun and some BeSO4-induced transformed cells possess neoplast ic potential resulting from genomic instability.