Abstract |
Betel quid (BQ) chewing has been associated with an increased risk of oral squamous cell carcinoma (OSCC) and oral submucous fibrosis (OSF). Piper betel 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 microM safrole in saliva). Safrole is a known rodent hepatocarcinogen, yet its carcinogenicity in human beings is largely undetermined. In this study, using a (32)P-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 (< 1/10(9) 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.
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Authors | C L Chen, C W Chi, K W Chang, T Y Liu |
Journal | Carcinogenesis
(Carcinogenesis)
Vol. 20
Issue 12
Pg. 2331-4
(Dec 1999)
ISSN: 0143-3334 [Print] England |
PMID | 10590228
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
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Topics |
- Areca
- Autoradiography
- Carcinoma, Squamous Cell
(etiology, genetics, metabolism)
- DNA Adducts
(metabolism)
- Humans
- Mouth Neoplasms
(etiology, genetics, metabolism)
- Plants, Medicinal
- Safrole
(chemistry)
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