Fibroblast growth factor-2 (FGF-2) is a multifunctional factor which is found in 21-25 kDa high molecular weight (HMW), or 16-18 kDa low molecular weight (LMW) forms, resulting from translation initiation from unconventional CUG- or conventional AUG- start sites, respectively. Previous studies have demonstrated that rat HMW- but not LMW-FGF-2, introduced into cardiac myocytes by gene transfer, caused a distinct nuclear phenotype, characterized by condensed chromatin and formation of several DNA 'clumps' inside the nucleus. In the present study we investigated first whether human HMW FGF-2, sharing 82% homology with its rat counterpart at the CUG-initiated extension, was also capable of eliciting the same phenotype as rat HMW FGF-2. Secondly, we investigated whether the mechanism of chromatin condensation and separation caused by HMW FGF-2 engaged an apoptosis-like, mechanism. Finally, we examined whether the HMW FGF-2 induced nuclear phenotype resulted from a mitosis-like mechanism. (Abstract shortened by UMI.)