The catechins, (-)-epicatechin (EC), (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECG) and (-)-epigallocatechin gallate (EGCG) are believed to be active constituents of green tea accounting for the reported chemoprevention of certain cancers. The molecular mechanisms by which the measured low concentrations (ca. micromolar) of catechins in humans can reduce the incidence of carcinogenesis is not clear. Using an in vitro plasmid DNA system and radiolytically generating reactive oxygen species (ROS) under constant scavenging conditions, we have shown that all four catechins, when present at low concentrations, ameliorate free radical damage sustained by DNA. A reduction in both prompt DNA single-strand breaks and residual damage to the DNA bases, detected by subsequent incubation with the DNA glycosylases formamidopyrimidine (FPG), endonuclease III (EndoIII) and 5' AP endonuclease exonuclease III (ExoIII), was observed. EGCG was found to be the most active of the catechins, with effects seen at micromolar concentrations. Combined fast-reaction chemistry studies support a mechanism of electron transfer (or H-atom transfer) from catechins to ROS-induced radical sites on the DNA. These results support an antioxidant role for catechins in their direct interaction with DNA radicals.

This study analyzed student characteristics that impact persistence among first-year students attending a large, metropolitan community college. The Cooperative Institutional Research Program (CIRP) Freshmen Survey was administered to first-time students during orientation. Factor analysis was used to classify students' personality and behavioral characteristics and discriminant function analysis was used to predict retention or attrition. The discriminant model accurately predicted retention in 78.8% of the cases. Findings suggested that student characteristics impacting persistence can be classified into three categories: barriers, motivations and aspirations, and expectations. Among the strongest predictors of attrition were the number of developmental classes required, the intention to transfer to a four-year institution, and the expectation that English as a second language could be a problem for college students. Among the strongest predictors of persistence were being African American or Latino, cumulative GPA, and the length of time students plan to spend at the college. Recommendations are shared for how community college administration, faculty, and staff can work with students and the community to raise student expectations, motivation, and preparation long before they become first-year college students. 117

Dopamine (DA) and uric acid (UA) have been found to undergo a protective reaction effecting the fast chemical repair of oxidative free-radical damage to DNA. This antioxidant reaction does not occur with normal concentrations of other, more abundant, antioxidants and our findings suggest that DA and UA are important for the preservation of the DNA in certain brains cells per se. These studies point to the need for drugs that undergo a similar antioxidant reaction with DNA radicals to prevent or arrest DNA damage associated with Parkinson's disease when the levels of DA and UA fall.

Targeting the anticancer compound tirapazamine (3-amino-1,2,4-benzotriazine 1,4-dioxide; TPZ) to DNA by appended binding units has been found to greatly increase the free radical-induced production of both single and double strand breaks under hypoxia compared to TPZ itself. The (*)OH radical, produced upon the radiolysis of aqueous solutions, was used to damage plasmid DNA, and both types of strand breaks were quantified in the absence and presence of TPZ and analogues. Targeted analogues of TPZ show increases of 12-18-fold in single strand breaks, and 60-110-fold in double strand breaks, as compared with TPZ itself. The observed increased formation of double strand breaks under hypoxia is the likely mechanism for the large increase in potency previously demonstrated for a similarly targeted analogue of TPZ as a bioreductive drug (Delahoussaye et al. (2003) Biochem. Pharmacol. 65, 1807-1815). The one-electron reduction potential of the two-electron reduced metabolite of TPZ (the 1-oxide, SR 4317) has been measured as -568 +/- 9 mV, which is sufficiently high to oxidize carbon-centered radicals such as those formed on the sugar moiety of DNA. Targeting the 1-oxide moiety to DNA resulted in a ca. 50% increase in single strand breaks over that seen for TPZ without the dramatic increase in double strand breaks seen for the similarly targeted benzotriazine 1,4-dioxides. These studies support the mechanism by which the reduction of TPZ to an oxidizing radical leads to free radical damage on DNA that can be further oxidized by TPZ or SR4317 (and especially well by DNA-targeted analogues) to yield lesions resulting in strand breakage. The targeting of benzotriazine 1,4-dioxide analogues to DNA by appending binding units to the compounds thus represents an efficient system for inducing strand breaks in DNA.