Dose-related Increased Binding of Nickel to Chromatin Proteins; and Changes to DNA Concentration in the Liver of Guinea Pigs Treated with Nigerian Light Crude Oil

The alteration in nuclear DNA concentration and the concomitant binding of xenobiotics (alkylating agents, heavy metals, etc.) to chromatin constituents may adversely affect gene structure and/or function, and thus initiate carcinogenesis. Binding of nickel to chromatin DNA has been reported to cause DNA damage (cross-links, single-strand breaks), and although many soluble nickel compounds and complexes have been shown to bind to chromatin, porphyrin-complexed nickel (PCN) in crude oils has not been studied. We have determined the dose-related increases in total and chromatin DNA concentrations, and the differential distribution (binding) of PCN (crude oil nickel-CON) to chromatin constituents in livers of adult male guinea pigs treated with 1.25, 2.50 and 5.0 ml/kg bw Nigerian Bonny light crude oil (BLCO) by intraperitoneal injection. The results showed large BLCO-induced increases in total DNA concentrations of 424%, 632% and 436% at 1.25, 2.50 and 5.0 ml/kg bw BLCO respectively over the untreated controls; while it induced equally large increases in chromatin DNA concentrations of 585% and 200% at 2.50 and 5.0 ml/kg bw respectively. In both cases, maximum increases occurred at 2.50 ml/kg bw BLCO. The distribution of PCN in BLCO between chromatin DNA and chromatin proteins (histones and non-histones) showed that at 2.50 and 5.0 ml/kg bw BLCO, nickel content in chromatin DNA reduced by 25% and 12.5% respectively over the controls; while its content in chromatin proteins also reduced by 26%; but increased by 166% at 2.50 and 5.0 ml/kg bw BLCO, respectively over the untreated controls. However, in intra-chromatin comparison, 38.8% more PCN bound to chromatin DNA than to chromatin proteins at 2.50 ml/kg bw; but at 5.0 ml/kg bw BLCO, 90.4% more PCN bound to chromatin proteins than to chromatin DNA. These results show a greater affinity of PCN in BLCO for chromatin proteins over chromatin DNA which may have played a role in the increased DNA concentrations. Also, the results may add critical information to understanding the reactions of porphyrin-complexed nickel in crude oils with chromatin since this has not been studied before. Furthermore, the probable carcinogenicity of BLCO may be implied.