Safrole-like DNA adducts in oral tissue from oral cancer patients with a betel quid chewing history

• Published in: Carcinogenesis (New York) Vol. 20; no. 12; pp. 2331 - 2334
• Main Authors: Chen, Chiu-Lan, Chi, Chin-Wen, Chang, Kuo-Wei, Liu, Tsung-Yun
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.12.1999; Oxford Publishing Limited (England)
• Subjects: 2′-deoxyadenosine 3′-monophosphate; 2′-deoxyguanosine 3′-monophosphate; 3′-phosphoadenosine 5′-phosphosulfate; Areca; Autoradiography; betel quid; Biological and medical sciences; Carcinoma, Squamous Cell - etiology; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - metabolism; dAMP; dGMP; DNA Adducts - metabolism; Humans; Medical sciences; Mouth Neoplasms - etiology; Mouth Neoplasms - genetics; Mouth Neoplasms - metabolism; NCMT; non-cancerous matched tissue; oral squamous cell carcinoma; oral submucous fibrosis; OSCC; OSF; Otorhinolaryngology. Stomatology; PAPS; Plants, Medicinal; safrole; Safrole - chemistry; Tumors; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology; Asia; Taiwan; Human; Drug addiction; Squamous cell carcinoma; Toxicity; Piperaceae; Betel; Malignant tumor; Safrole; Carcinogen; Oral cavity; Chewing gum; Dicotyledones; DNA; Angiospermae; Fibrosis; Plant origin; ENT disease; Submucosa; Spermatophyta; Piper; Molecular adduct
• ISSN: 0143-3334; 1460-2180
• DOI: 10.1093/carcin/20.12.2331

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.