Carcinogenesis, Vol. 20, No. 12, 2331-2334,
December 1999
© 1999 Oxford University Press
Short Communications |
Safrole-like DNA adducts in oral tissue from oral cancer patients with a betel quid chewing history
1 Institute of Pharmacology and
2 Institute of Oral Biology, National Yang-Ming University and
3 Department of Medical Research and Education, Veterans General Hospital–Taipei, Taipei, Taiwan, Republic of China
Betel quid (BQ) chewing has been associated with an increased risk of oral squamous cell carcinoma (OSCC) and oral submucous fibrosis (OSF). Piper betle inflorescence, which contains 15 mg/g safrole, is a unique ingredient of BQ in Taiwan. Chewing such prepared BQ may contribute to safrole exposure in human beings (420 µM safrole in saliva). Safrole is a known rodent hepatocarcinogen, yet its carcinogenicity in human beings is largely undetermined. In this study, using a 32P-post-labeling method, we have found a high frequency of safrole-like DNA adducts in BQ-associated OSCC (77%, 23/30) and non-cancerous matched tissue (NCMT) (97%, 29/30). This was in contrast to the absence (< 1/109 nucleotides) of such adducts in all of non-BQ-associated OSCC and their paired NCMT (P < 0.001). Six of seven OSF also exhibited the same safrole-like DNA adduct. The DNA adduct levels in OSF and NCMT were significantly higher than in OSCC (P < 0.05). Using co-chromatography and rechromatography techniques, we further demonstrated that these adducts were identical to synthetic safrole–dGMP adducts as well as DNA adducts from 1'-hydroxysafrole-treated HepG2 cells. These results suggest that safrole forms stable safrole–DNA adducts in human oral tissue following BQ chewing, which may contribute to oral carcinogenesis.
Abbreviations: BQ, betel quid; dAMP, 2'-deoxyadenosine 3'-monophosphate; dGMP, 2'-deoxyguanosine 3'-monophosphate; NCMT, non-cancerous matched tissue; OSCC, oral squamous cell carcinoma; OSF, oral submucous fibrosis; PAPS, 3'-phosphoadenosine 5'-phosphosulfate.
4 To whom correspondence should be addressed at: Department of Medical Research and Education, Veterans General Hospital-Taipei, Taipei, Taiwan 11217, Republic of China Email: tyliu{at}vghtpe.gov.tw
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