Paraxanthine/Caffeine Ratio: as an Index for Cypia2 Activity in Polycyclic Aromatic Hydrocarbons Exposed Subjects

Abstract

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous in the environment

and originated from incomplete combustion process of organic materials. This

compounds are bioactivated to reactive metabolites which bind covalently to DNA

initiating carcinogenesis. PAHs have been well established as an enzyme inducer of

cytochrome P450 (CYP) such as CYP1A1 and CYP1A2. Caffeine is primarily

metabolized by CYP1A2 to paraxanthine, so it has been used as a specific probe for

assessing CYP1A2 activity. The purpose of this study was to compare CYPIA2

activity in female subjects between smoke and non- smoke exposure using serum

paraxanthine/caffeine ratio. Each subject took a 180 mg single oral dose of caffeine

solution. Blood samples were collected before and 5 hours after caffeine intake. The

serum was separated by centrifugation and stored at -20 °C until analysis by HPLC.

Carbonmonoxide (CO) level in blood was also detected using spectrophotometer. The

results showed that serum paraxanthine/caffeine ratio in exposed subjects was

significantly higher than non-exposed subjects (mean ± SD of 0.45 ± 0.18 and 0.33 ±

0.12, respectively; P< 0.05). CO level in exposed subjects was also significantly

higher than non-exposed subjects (mean ± SD of 4.02 ± 0.83 and 3.00 ± 0.72,

respectively, P< 0.05). Conclusion: By using paraxanthine/caffeine ratio as a probe,

CYP1A2 activity is increased in smoke exposed subjects. The result implies that these

subjects has exposed to PAHs and has more risk of carcinogenesis.