Carcinogenic potential and genomic instability of beryllium sulphate in BALB/c-3T3 cells.
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. BALB/c-3T3 cells were treated with varying concentrations of BeSO4 for 72 h and the transformation frequency was determined after 4 weeks of culturing. Concentrations from 50-200 microg 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 by BeSO4 were 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 BALB/c-3T3 cells 90 days post-injection. Gene amplification 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 fingerprinting was employed to detect genomic instability. Gene amplification was found in K-ras and c-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 BeSO4 is capable of inducing morphological cell transformation in mammalian cells and that transformed cells induced by BeSO4 are potentially tumorigenic. Also, cell transformation induced by BeSO4 may be attributed, in part, to the gene amplification of K-ras and c-jun and some BeSO4-induced transformed cells possess neoplastic potential resulting from genomic instability.
Keshava
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N
Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, West Virginia 26505-2845, USA.
Zhou
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G
Spruill
M
M
Ensell
M
M
Ong
T M
TM
D016475:3T3 Cells; D000818:Animals; D001608:Beryllium / Q000494:pharmacology*; D015197:Carcinogenicity Tests; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D005354:Fibrosarcoma; D005784:Gene Amplification / Q000187:drug effects; D016758:Genes, jun / Q000235:genetics; D011905:Genes, ras / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009154:Mutation / Q000187:drug effects; D009374:Neoplasms, Experimental; D019105:Random Amplified Polymorphic DNA Technique
C020711:beryllium sulfate; D001608:Beryllium