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The role of lime in the formation of reactive oxygen species (ROS), i.e, O°H202, 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.

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DNA double-strand breaks (DSB) are considered the critical primary lesion in the formation of chromosomal aberrations (CA). DSB occur spontaneously during the cell cycle and are induced by a variety of exogenous agents such as ionising radiation. To combat this potentially lethal damage, two related repair pathways, namely homologous recombination (HR) and non-homologous DNA end joining (NHEJ), have evolved, both of which are well conserved from bacteria to humans. Depending on the pathway used, the underlying mechanisms are capable of eliminating DSB without alterations to the original genomic sequence (error-free) but also may induce small scale mutations (base pair substitutions, deletions and/or insertions) and gross CA (error-prone). In this paper, we review the major pathways of DSB-repair, the proteins involved therein and their impact on the prevention of CA formation and carcinogenesis.