[Alteration of FHIT gene and p16 gene in malignant transformed cells induced by crystalline nickel sulfide].
OBJECTIVE
To detect the alteration of fragile histidine triad (FHIT) gene and p16 gene during malignant transformation of immortal human bronchial epithelial cell line (16HBE) induced by crystalline nickel sulfide, and study the molecular mechanism of nickel carcinogenesis.


METHODS
Malignant transformed cells and tumorigenic cells were examined for the alteration of FHIT gene and p16 gene by RT-PCR, DNA sequencing and silver staining PCR-SSCP.


RESULTS
Compared with those of control 16HBE, neither mutation of exon2 or exon2-3, abnormal expression in p16 gene nor mutation of FHIT exon5, 6, 7 and 8, exon1-4 or exon5-9 were observed in transformed cells and tumorigenic cells. But aberrant transcript or FHIT gene expression loss were observed in transformed cells and tumorigenic cells. One of the aberrant transcripts in FHIT gene, the deletion of exon6, exon7 and exon8 and an insertion of 36 bp sequence replacing exon6-8, was confirmed by sequencing.


CONCLUSIONS
FHIT gene, not p16 gene, could play a definite role in nickel carcinogenesis. Alterations of FHIT gene induced by crystalline NiS could be a molecular event associated with carcinogen, chromosome fragile site instability and cell malignant transformation, and FHIT gene could be one of the important target genes activated by exotic carcinogens.
Ji
Wei-dong
WD
Institute for Chemical Carcinogenesis, Guangzhou Medical College, Guangzhou 510182, China.
Wu
Zhong-liang
ZL
Chen
Jia-kun
JK
Yi
Fei
F
Feng
Su-mei
SM
D017766:Acid Anhydride Hydrolases; D001483:Base Sequence; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000378:metabolism*; D002478:Cells, Cultured; D015870:Gene Expression; D019942:Genes, p16 / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009532:Nickel / Q000494:pharmacology*; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D009363:Neoplasm Proteins; D009532:Nickel; D000099170:Bis(5'-adenosyl)triphosphatase; C017558:nickel sulfide