DNA damage induced by areca exposure in esophageal cancer-detection of safrole DNA adduct in tissue from esophageal cancer.
aDepartment of Surgery, National Taiwan University Hospital, National Taiwan, , bGraduate Institute of Occupational Health and Safty, Kauhsiung Medical University, Kauhsiung Medical, , cDepartment of Medical Research and Education, Veteran General Hospital
Recently, areca quid chewing has been demonstrated to be an independent risk factor for developing esophageal cancer in the Indian and Taiwanese population. AIM AND METHODS: Since areca quid contains safrole and unidentified substances, which pose carcinogenic potential to human beings, we analyzed the safrole-DNA adduct by the 32P-postlabeling. RESULTS: Totally, we 45 evaluated patients of esophageal cancer who received esophagectomy in National Taiwan University Hospital in Taiwan. Among the individuals with a history of habitual areca chewing (n=19), one (5%) of the tumor tissue and 5 (25%) normal esophageal mucosa was positive for safrole-DNA adduct. The adduct can not be detected in the cigarette smokers or alcohol drinkers who did not consumed areca (n=20). The individuals who were abstained from these three substances were also negative adducts detection (n=6) (p< 0.001 as comparing the individual with or without areca chewing). To confirm the nature of this adduct, we first synthesized the safrole-dG adduct and confirmed it by the HPLC/MS, and then mix this adduct with the samples and assayed by the 32P-postlabeling. It revealed that the synthetic safrole-dG adduct was identical with that presented in esophageal cancer samples. Finally, in the esophageal epithelium possessing the ability to metabolize the safrole, the cellular safrole DNA-adduct formation can be further enhanced by treatment with the cytochrome P450 inducer, 3 MC, and followed by incubation with safrole (10 mM) for 24 hours. CONCLUSION: Our study indicated that the esophageal carcinogenic effect of areca quid is at least partly due to the safrole-associated DNA damaged where Piper betel inflorescence is used in preparation of the areca quid.
Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Nice, France; February 7 - 10, 2004; in poster session 996 (Genetic & environmental interactions).