J Med Assoc Thai 2003; 86 (6):310

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Paraxanthine/Caffeine Ratio : As an Index for CYP1A2 Activity in Polycyclic Aromatic Hydrocarbons Exposed Subjects
Wittayalertpanya S Mail, Hinsui Y , Lawanprasert S

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous in the environment and originate
from incomplete combustion process of organic materials. These compounds are bioactivated to
reactive metabolites which bind covalently to DNA and subsequently initiate 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 CYP1A2
activity in female subjects that were automobile exhaust exposed and non-automobile exhaust exposed
using serum paraxanthine/caffeine ratio as an index. Each subject took a 180 mg single oral dose of
caffeine solution. Blood samples were collected before and 5 hours after caffeine intake. Serum samples
were separated by centrifugation and stored at -20"C until analysis by high performance liquid chro-
matography (HPLC). Carbon monoxide (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 เธ‘ SE of 0.45 เธ‘ 0.05 and 0.33 เธ‘ 0.03, respectively; p
<
0.05). CO
level in exposed subjects was also significantly higher than non-exposed subjects (mean เธ‘ SE of 4.03 เธ‘
0.21 and 3.01
เธ‘
0.18, respectively; p
<
0.05). Conclusion: Paraxanthine/caffeine ratio, as an index for
CYP1A2 activity, can be used to determine PAHs exposure. Automobile exhaust exposed subjects
demonstrated significantly higher CYPIA2 activity than that of the non-exposed subjects. Exposed
subjects have a possibly higher risk of chemical carcinogenesis.
Key word : Paraxanthine/Caffeine Ratio, CYP1A2, PAHs

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