Lymphocyte ascorbate concentrations

If the prevention of oxidative DNA damage plays an important role in the cancer chemopreventive effects of dietary antioxidants, then one would expect to see an inverse relationship between antioxidant intake and biomarkers of oxidative DNA damage. Lymphocyte ascorbate concentrations were inversely associated with lymphocyte 8-oxodG concentrations in 105 men and women (r=-0.28)." However, plasma concentrations of a-tocopherol and carotenoids were positively correlated with lymphocyte concentrations of 8-oxodG in a study of 52 healthy women (r=0.29 to... 

It should be remembered that some of the established antioxidants have other metabolic roles apart from free-radical scavenging. The finding of reduced antioxidant defences in diabetes, for example, may not be prima fascie evidence of increased oxidative stress, since alternative explanations may operate. For example, this may reflect a response to reduced free-radical activity as su ested by the results of a previous study (Collier et al., 1988). In the case of ascorbate, an alternative explanation has been proposed by Davis etal. (1983), who demonstrated competitive inhibition of ascorbate uptake by glucose into human lymphocytes. This view is supported by the similar molecular structure of glucose and ascorbic acid (see Fig. 12.4) and by a report of an inverse relationship between glycaemic control and ascorbate concentrations in experimental diabetes in rats. Other investigators, however, have not demonstrated this relationship (Som etal., 1981 Sinclair etal., 1991). 

Lymphocyte performance is known to be affected by ascorbate concentration. For instance, Cameron et aL (1979) reported an enhancement in immunocompe-tence upon saturation of lymphocytes with ascorbate. Both in vitro and in vivo studies have indicated an immunostimulatory effect of ascorbate on lymphocytic cells (references cited in Jariwalla and Harakeh, 1994). 

Literature data on cytotoxic effects of photoexcited fullerene C60 are controversial. In the studies on transformed B-lymphocytes of Raji fine, phototoxic action of water-soluble carboxy-C60 was not revealed even upon its concentration of 5 x 10 5 M (Irie et al., 1996). In the study (Kamat et al., 2000) damaging effect of fullerenes C60 in dependence on intensity of irradiation toward CHO cells has been demonstrated. Using microsomal fraction of rat liver that was treated with C -cyclodextrin complex, it was shown that already in 5-30 min after UV-irradiation the accumulation of LPO products occurs that is suppressed by antioxidants like ascorbic acid and a-tocopherol. Similar effect of fullerenes C60 has been revealed in microsomal fraction of the cells of ascitic sarcoma 180 (Kamat et al., 2000). 

The blood erythrocyte count is increased in smokers. The amount of carboxyhemoglobin may exceed 10% of the total hemoglobin in heavy smokers, and the increased number of cells compensates for impaired ability of the red cells to transport oxygen. The blood PO2 of the habitual smoker is usually about 5 mmHg (0.7 kPa) less than in the nonsmoker, whereas the PCO2 is unaffected. The blood leukocyte concentration is increased by as much as 30% in smokers, but the leukocyte concentration of ascorbic acid is greatly reduced. The lymphocyte count is increased as a proportion of the total leukocyte count. 

Ascorbic Acid Deficiency. Scurvy is the classical disease associated with ascorbate deficiency. It is a disease of the connective tissue and probably is caused by inadequate crosslinking attributed to a lack of hydroxy-lated proline and lysine. Many consider scurvy to be an advanced stage of ascorbate deficiency. Chronic deficiencies may also (l)in-crease risk for malignancies, as evidenced by oxidized DNA markers and increased concentrations of reactive oxygen species (2) decreased immune function, as evidenced by less vitamin in neutrophils and lymphocytes (3) cardiovascular disease caused by the inflammatory response on the blood vessel walls and (4) cataract formation caused by decreased concentrations of ascorbate in the ocular tissues. 

The current recommended dietary allowance (RDA) for vitamin C (L-ascor-bate) for adult non-smoking individuals is 60 mg day which is based on a mean requirement of 46 mg day to prevent the deficiency disease scurvy [ 14]. It was shown that ascorbate uptake by neutrophils, monocytes, and lymphocytes saturate with a daily supplementation of 100 mg ascorbate and that these cells contain concentrations at least 14-fold higher than those in plasma. Bioavailability was complete for 200 mg of vitamin C as a single dose. 

A few studies have used the Comet assay to examine the association between plasma antioxidant concentrations and oxidative DNA damage. One study of healthy, nonsmoking men and women from Madrid found oxidized pyrimidines, but not altered purines, in lymphocyte DNA to be inversely associated with plasma (3-carotene, lutein, and total carotenoid concentrations (r=-0.4)." Neither plasma vitamin C nor vitamin E concentrations were significantly associated with oxidized pyrimidines or altered purines in lymphocyte DNA. A smaller study of 11 healthy Slovakian men followed monthly for one year found only plasma lycopene concentrations to be inversely associated with oxidized pyrimidines in lymphocyte DNA (i=-0.24), while plasma ascorbate... 

Because human immunodeficiency virus 1 (HIV-1) is consistently associated with AIDS (9-12), we investigated the action of ascorbate on HIV infection under controlled conditions in vitro. Here, we report the effects of ascorbate on acutely and chronically HIV-infected T-lymphocytic cell lines grown continuously in the presence of nontoxic concentrations of the compound. In addition, we report the action of ascorbate on cell-free virus particles in vitro. 

Effect of Ascorbate on Vims Replication in Freshly Infected Cells, To extend these findings to freshly infected cells, we investigated the effects of ascorbate on acute HIV infection of susceptible CIW T lymphocytes. Viral infectivity and cytopathic effect in these cells have been correlated with formation of giant cell syncytia mediated by interaction of HIV envelope glycoprotein with CD4 cell surface receptor (14, 20, 21). In controls, multinucleated syncytia became visible by day 4 and reached high levels on day 6. The continuous presence of ascorbate caused a dose- and time-dependent decrease in syncytium formation. On day 4, 93.3% inhibition in syncytia number was seen with ascorbate at 100 /tg/ml (Fig. 6). At this concentration, ascorbate did not inhibit the growth of uninfected VB cells (99% survival by trypan blue dye exclusion), indicating that the... 

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