Metabolic activations of polycyclic hydrocarbons. Structure-activity relationships

Area of Science:

• Environmental Chemistry
• Toxicology
• Computational Chemistry

Background:

• Benzo(a)-pyrene's ultimate carcinogenic forms are identified as 7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrenes.
• Polycyclic Aromatic Hydrocarbons (PAHs) are environmental pollutants with known mutagenic and carcinogenic potential.

Purpose of the Study:

• To assess the general role of diol epoxides in PAH mutagenesis and carcinogenesis using quantum mechanical calculations.
• To predict the relative reactivity of diol epoxides derived from various PAHs.

Main Methods:

• Quantum mechanical calculations were employed to determine the ease of carbonium ion formation in diol epoxides.
• Calculated reactivity was correlated with experimental mutagenicity data for diol epoxides.

Main Results:

• The calculated reactivity of diol epoxides serves as a reliable predictor of their mutagenicity.
• Metabolic activation and mutagenicity of benzo(a)anthracene dihydrodiol derivatives and diol epoxides were investigated.

Conclusions:

• Quantum chemical calculations offer a valuable tool for predicting the mutagenic potential of PAH metabolites.
• The study highlights the importance of diol epoxides in PAH-induced carcinogenesis and discusses limitations of predictive models.