Nickel(II) induces microsatellite mutations in human lung cancer cell lines

Nickel(II) is a human carcinogen causing respiratory cancers. The purpose o f this study was to determine whether Ni(II) may induce microsatellite muta tions in human cells. We transfected the three human lung tumor cell lines A427, HCC15 and NCI-H2009 with a mammalian expression vector containing a ( CA)(13) repeat in the coding sequences of the reporter hygromycin gene (hyg ). A total of 33 clones carrying the integrated vector derived from the thr ee cell Lines was investigated for spontaneous and Ni(II)-induced hygromyci n-resistant (hyg(r)) reversion mutants. Significantly higher frequencies of hyg(r) reversion mutations were observed in Ni(II)-treated cells (NCI-H200 9 and HCC-15) than control cells. In the majority of the colonies hyg(r) ph enotype was due to mutations within the integrated (CA) repeat sequence. Th e type of mutations consisted of both contraction and expansion of the (CA) repeat unit. The finding that Ni(II) promotes microsatellite mutations rai ses the possibility that genetic instability may be a mechanism involved in nickel carcinogenesis. (C) 2000 Elsevier Science B.V. All rights reserved.