Adenosine diphosphate ribosyl transferase responses to a standardized dose of hydrogen peroxide in the mononuclear leukocytes of patients with a diagnosis of cancer

Abstract

Mononuclear leukocytes from 151 patients with cancer of various organs and from 467 apparently cancer-free individuals were exposed, in vitro, to H2O2 (100 microM) and the effects of the exposure on the activity of adenosine diphosphate ribosyl transferase (ADPRT) were determined. First, the reproducibility of this test procedure was established as satisfactory, by comparing the results of assays performed independently by two investigators, and by measuring ADPRT in cells from two individuals over a 9-week period. The test data were analyzed by multiple linear regression, and the correlation of cancer diagnosis, age, sex and smoking habits with ADPRT values was determined. The strongest correlate was cancer diagnosis. We considered categorizing ADPRT values as high and low, with a cut-off value that would substantially distinguish cancer from cancer-free individuals. When a cut-off value of 1200 c.p.m. TCA ppt [3H]NAD+/5 x 10(5) cells was applied to the complete test material, it was found that ADPRT values from cancer patients were more frequently below the cut-off than values from disease-free individuals: the relative risk estimate (odds ratio) was 13.8. When a similar analysis was done on values from lung cancer patients and smoking disease-free individuals, the odds ratio was 73.5. However, a cut-off value of 2000 c.p.m. TCA ppt [3H]NAD+/5 x 10(5) cells was most effective in distinguishing lung cancer patients (the largest cancer group, n = 96) from smoking non-cancer individuals: that value provided better sensitivity (85%) and specificity (81%) than other cut-off values tested in the range 1200-2000 c.p.m. Further, in the case of lung cancer, possible effects of anatomical site, and of staging and pathology on ADPRT values was analyzed by the chi-squared test: no significant associations were found. These data support the value of the ADPRT test in detecting early stage lung cancer regardless of location or pathological type.

Reduced poly(ADP‐ribosyl)ation in lymphocytes of laryngeal cancer patients: Results of a case‐control study

“…A reduced PARP response to DNA-damaging agents was previously found in patients with miscellaneous cancers (lung, brain, colon), 28 breast cancer 29 and familial adenomatous polyposis. 30 PARP activity is affected by factors such as age, smoking and inflammation.…”

“…Our results showed that there was significantly less bleomycininduced PARP activity in peripheral blood lymphocytes from laryngeal tumor patients than in healthy controls, while basal activity was not significantly different. A reduced PARP response to DNA-damaging agents was previously found in patients with miscellaneous cancers (lung, brain, colon), 28 breast cancer 29 and familial adenomatous polyposis. 30 PARP activity is affected by factors such as age, smoking and inflammation.…”

Effect of dna repair gene polymorphisms on BPDE‐DNA adducts in human lymphocytes

“…Its role in terms of repair in lymphocytes is unclear at present. It is possible to hypothesize that it might influence DNA repair activity through, for instance, excessive endogenously generated oxidative stress, which in turn might affect lymphocytes and their repair values, 30,31 flattening the differences among the analyzed genotypes with possibly different repair efficiency.…”

The Genetic Regulation of ADPRT/PARP-1 in Aging and Cancer Susceptibility

“…As shown in Table 2, lower ADPRT/PARP-1 expression and enzyme activity in peripheral lymphocytes were observed in cancer patients compared to controls [Pero et al, 1989;Bieche et al, 1996;Hu et al, 1997;Cristovao et al, 1998;RajaeeBehbahani et al, 2002]. In a study of various cancers, the ADPRT/PARP-1 enzyme activity in lymphocytes was approximately 57% of that in controls [Pero et al, 1989]. Subjects with low levels of H 2 O 2 -induced ADPRT/PARP-1 activity had a 12.1-fold increased risk for developing cancer [Pero et al, 1989].…”

“…In a study of various cancers, the ADPRT/PARP-1 enzyme activity in lymphocytes was approximately 57% of that in controls [Pero et al, 1989]. Subjects with low levels of H 2 O 2 -induced ADPRT/PARP-1 activity had a 12.1-fold increased risk for developing cancer [Pero et al, 1989]. In a breast cancer case-control study, cases had a lower constitutive and H 2 O 2 -induced enzyme activity.…”