High blood pressure related to carcinogen-induced unscheduled DNA synthesis, DNA carcinogen binding, and chromosomal aberrations in human lymphocytes.

ABSTRACT

Unscheduled DNA synthesis (excision-repair) of N-acetoxy-2-acetylaminofluorene (NA-AAF) damage to the DNA of human lymphocytes was determined quantitatively for 92 individuals with diastolic blood pressures ranging from 65 to 120 mm of Hg (8,7 to 16 kPa). Measurements of NA-AAF-induced repair synthesis (incorporation of[3H]thymidine in the presence of 10 mM hydroxyurea) showed linear increase with the blood pressure in the individuals under study. Concurrent determinations for the levels of 3H-labeled 7,12-dimethyl-benz[a]anthracene bound to the DNAs of lymphocytes after 18 hr of culturing have shown that increased amounts of DNA bound carcinogen were linearly proportional to increased NA-AAF-induced repair synthesis values, and therefore were correlated to high blood pressure. The number of NA-AAF-induced chromosomal abberations in lymphocytes increased linearly with the diastolic blood pressures of the individuals. High NA-AAF-induced repair synthesis values also tended to be associated with increased NA-AAF-induced chromosomal damage. Together, these results suggest that individuals with elevated blood pressures have a greater potential for accumulating DNA damage, because of an increased chemical reactivity of lymphocytes to carcinogen exposure, than do individuals with normal blood pressure.