Evaluation of DNA damage in jewellery workers occupationally exposed to nitric oxide

Abstract

Nitric oxide is a metastable radical, reacts with oxygen to produce toxic nitrogen oxides (N₂O₃, ONOO⁻) which damage DNA. Occupational exposure to nitric oxide leads to increased frequency of chromosomal aberrations in humans. In the present study the DNA damage among the jewellery workers occupationally exposed to nitric oxide was analyzed using buccal cell comet assay. The result of this study shows increased levels of DNA damage among jewellery workers. The habit of cigarette smoking among the jewellery workers has a synergistic effect on inducing DNA damage.

Introduction

Gold and its alloys are commonly used in making jewellery and coins. During this process gold is dissolved in a mixture of solution containing concentrated nitric acid and hydrochloric acid (aqua regia). Nitric acid dissolves the gold and forms Au³⁺ ions, chloride ions from hydrochloric acid reacts with gold to produce chloaurate anions. Further oxidation takes place in the solution and the gold is dissolved. During this process, NO radical (NO) is produced. The jewellery workers are occupationally exposed to NO during the purification of gold and silver. NO reacts with oxygen to form reactive nitrogen oxide intermediates (RNOS*) which have shown to damage DNA molecules (Nguyen et al., 1992). It is a member of reactive nitrogen species (RNS) and is capable of producing nitration, nitrosation and deamination reactions on DNA bases and hence it is considered as a potent mutagenic agent (Oshima and Bartsch, 1994). NO is a strong oxidant which stimulates DNA damage by inhibiting DNA repair enzymes and DNA ligases (Laval et al., 1997, Graziewicz et al., 1996).

NO reacts with oxygen and superoxide to toxic nitrogen oxides (N₂O₃, ONOO⁻) which are more reactive than NO and causes diverse chemical reactions in biological systems including nitration of tyrosine residues of proteins, triggering of lipid peroxidation, inactivation of aconitases, inhibition of mitochondrial electron transport and oxidation of biological thiol compounds (Beckman et al., 1990, Maeda and Akaike, 1998). The possible mechanisms of DNA damage induced by NO are: (i) formation of carcinogenic nitrosamines; (ii) direct modification of DNA by RNOS; and (iii) inhibition of systems required to repair DNA lesions mediated by other genotoxic substances (Wink et al., 1998). NO is considered as a tumor initiating agent and involved in cancer development (Li and Hotchkiss, 1995, Hogg et al., 1996). In lung cancer patients an altered NO metabolism and increased levels of NO and nitrite was identified (Masri et al., 2005). An increased level of NO was also identified in the patients of oral cancer, head and neck cancer, chronic obstructive pulmonary disease, arthritic disorders, asthma, Type 1 diabetes mellitus (Beevi et al., 2004, Gallo et al., 1998, Ichinose et al., 2000, Cuzzocrea, 2005, Maria et al., 2000, Kolb and Kolb-Bachofen, 1992). Hence the present study was carried out to assess the genotoxicity among jewellery workers who are occupationally exposed to NO.