Effect of co-existing biologically relevant molecules and ions on DNA photocleavage caused by pyrene and its derivatives.

Shuguang Wang,Hongtao Yu

doi:10.3390/ijerph2005010132

Shuguang Wang, Hongtao Yu

Open Access

https://doi.org/10.3390/ijerph2005010132

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Abstract

Inorganic ions, coenzymes, amino acids, and saccharides could co-exist with toxic environmental chemicals, such as polycyclic aromatic hydrocarbons (PAHs), in the cell. The presence of these co-existing chemicals can modulate the toxicity of the PAHs. One of the genotoxic effects by PAHs is light-induced cleavage, or photocleavage, of DNA. The effect of inorganic ions I-, Na+, Ca2+, Mg2+, Fe3+, Mn2+, Cu2+, and Zn2+ and biological molecules riboflavin, histidine, mannitol, nicotinamide adenine dinucleotide (NAD), glutathione, and glutamic acid on the DNA photocleavage by pyrene, 1-hydroxypyrene (1-HP), and 1-aminopyrene (1-AP), is studied. The non-transition metal ions Na+, Ca2+, and Mg2+, usually have very little inhibitory effects, while the transition metal ions Fe3+, Cu2+, and Zn2+ enhance, Mn2+ inhibits the DNA photocleavage. The effect by biological molecules is complex, depending on the photochemical reaction mechanisms of the compounds tested (1-AP, 1-HP and pyrene) and on the chemical nature of the added biological molecules. Riboflavin, histidine, and mannitol enhance DNA photocleavage by all three compounds, except that mannitol has no effect on the photocleavage of DNA by pyrene. Glutathione inhibits the DNA photocleavage by 1-AP and 1-HP, but has no effect on that by pyrene. NAD enhances the DNA photocleavage by 1-AP, but has no effect on that by 1-HP and pyrene. Glutamic acid enhances the DNA photocleavage by 1-AP and pyrene, but inhibits that by 1-HP. These results show that the co-existing chemicals may have a profound effect on the toxicity of PAHs, or possibly on the toxicity of many other chemicals. Therefore, if one studies the toxic effects of PAHs or other toxic chemicals, the effect of the co-existing chemicals or ions needs to be considered.

Highlights

Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental pollutants produced during forest fire, volcanic eruption, incomplete burning of fossil fuels, petroleum products, as well as during tobacco smoke, food processing, operation of machinery including automobiles, airplanes and ships [1,2]
Chemical carcinogenesis studies of PAHs started in 1915 when Yamagawa and Ichikawa observed that repeated application of coal tar on rabbits over extended periods induced skin carcinomas on the rabbit ears [3]
Since it is known that PAHs can cause light-induced DNA cleavage [15,16,17], they are photomutagenic toward Salmonella typhimurium bacteria strain TA102 [28], and genotoxic to human skin cells, the effect of co-existing chemicals on the light-induced DNA cleavage of PAHs is of interest to human health

Summary

Introduction

Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental pollutants produced during forest fire, volcanic eruption, incomplete burning of fossil fuels, petroleum products, as well as during tobacco smoke, food processing, operation of machinery including automobiles, airplanes and ships [1,2]. Further investigation of other carcinogenic components of coal tar by Cook et al led to the discovery of benzo[a]pyrene as one of the major carcinogenic components [5]. Since these pioneering studies, more than 30 PAHs and several hundred of their derivatives have been reported to exhibit some carcinogenic effects [6,7,8]. More than 30 PAHs and several hundred of their derivatives have been reported to exhibit some carcinogenic effects [6,7,8] It is reported in the 8th Report on Carcinogens that exposure to PAHs has been linked to the development of skin and lung cancers (National Toxicology Program, 1998)

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