title: Safrole-like DNA adducts in oral tissue from oral cancer patients with a betel quid chewing history.
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.
authors.affiliation: Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan, Republic of China.
authors.forename: C L
authors.initials: CL
authors.lastname: Chen
authors.forename: C W
authors.initials: CW
authors.lastname: Chi
authors.forename: K W
authors.initials: KW
authors.lastname: Chang
authors.forename: T Y
authors.initials: TY
authors.lastname: Liu
mesh_terms: D001114:Areca; D001345:Autoradiography; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D018736:DNA Adducts / Q000378:metabolism*; D006801:Humans; D009062:Mouth Neoplasms / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D010946:Plants, Medicinal; D012451:Safrole / Q000737:chemistry*
chemical_list: D018736:DNA Adducts; D012451:Safrole