Nair U J, Obe G, Friesen M, Goldberg M T, Bartsch H
International Agency for Research on Cancer, Lyon, France.
Environ Health Perspect. 1992 Nov;98:203-5. doi: 10.1289/ehp.9298203.
The role of lime in the formation of reactive oxygen species (ROS), i.e., O2-., H2O2, and OH., from betel-quid components (extracts of areca nut and catechu) was investigated in vitro using a chemiluminescence technique and an assay for oxidative DNA damage involving analysis of 8-hydroxy-2'-deoxyguanosine. Of the various areca-nut extracts, the catechin fraction, at alkaline pH, was shown to be the most active producer of ROS. The free Ca(OH)2 content and pH of lime samples (a component of betel quid and chewing tobacco) were highly correlated with the generation of ROS from areca-nut extract in vitro and with oxidative base damage to DNA in vitro. While Fe2+ had an enhancing effect on ROS formation, Mg2+ had a marked inhibitory effect. The cytogenetic effects of ROS generated in vivo were measured in Syrian golden hamsters in which the cheek pouch had been painted with lime and an areca-nut extract or catechu, singly or in combination. The frequency of micronucleated cells was increased only in animals that had received both the areca-nut extract and lime. The frequency of micronucleated cells in exfoliated oral mucosal cells from Indian chewers of betel quid with tobacco containing lime or of tobacco with lime was significantly higher than in a control (no habit) group. These studies demonstrate that addition of lime to betel quid constituents generates ROS, which induce cytogenetic damage in hamster cheek pouch and may contribute to the cytogenetic damage observed in the oral cavity of betel-quid chewers. These results implicate ROS in clastogenesis and probably in the etiology of oral cancer.
采用化学发光技术和一种涉及分析8-羟基-2'-脱氧鸟苷的氧化DNA损伤检测方法，在体外研究了石灰在槟榔成分（槟榔仁和儿茶提取物）形成活性氧（ROS）即超氧阴离子（O2-.）、过氧化氢（H2O2）和羟基自由基（OH.）中的作用。在各种槟榔提取物中，儿茶素部分在碱性pH条件下被证明是最活跃的ROS产生者。石灰样品（槟榔和嚼烟的一种成分）中的游离Ca(OH)2含量和pH与体外槟榔提取物产生ROS以及体外DNA氧化碱基损伤高度相关。虽然Fe2+对ROS形成有增强作用，但Mg2+有显著抑制作用。在叙利亚金仓鼠体内测量了体内产生的ROS的细胞遗传学效应，在这些仓鼠的颊囊上单独或联合涂抹石灰、槟榔提取物或儿茶素。仅在同时接受槟榔提取物和石灰的动物中，微核细胞频率增加。来自印度咀嚼含石灰槟榔或含石灰烟草的槟榔咀嚼者的脱落口腔黏膜细胞中的微核细胞频率显著高于对照组（无此习惯组）。这些研究表明，在槟榔成分中添加石灰会产生活性氧，其可诱导仓鼠颊囊细胞遗传学损伤，并可能导致槟榔咀嚼者口腔中观察到的细胞遗传学损伤。这些结果表明活性氧与染色体断裂有关，可能也与口腔癌的病因有关。
