Background levels of DNA damage in the population.

Abstract

In addition to the dangers of man-made mutagenic substances, there exist a variety of naturally-occurring agents and processes than can cause DNA damage in man. These include exogenous agents, such as sunlight and dietary mutagens, as well as endogenous agents, such as reactive oxygen species which are formed within the cell via normal metabolism. These processes can lead to at least six major types of DNA damage: base loss, base deamination, base alkylation, base dimerization, base oxidation, and single-strand breakage. Based upon in vitro measurements in cell-free model systems or cultured cells, estimates of the rates of production of these lesions have been made for the average human cell: about 26,000 base losses per day, primarily purines lost because of spontaneous hydrolysis of the glycosyl bond; about 350 cytosine deaminations per day; tens of thousands of base alkylations per day, primarily methylations of guanine caused by S-adenosylmethionine; up to 50,000 pyrimidine dimerizations per day, dependent upon exposure to sunlight; and about 100,000 single-strand breaks per day. Based upon measurements of DNA oxidation products in human urine, we estimate that the total rate of formation of all oxidative DNA damage products in man is on the order of a few thousand events per cell per day. In addition, base mispairing can take place in the absence of DNA damage because of tautomeric shifts, base ionization, or base rotation.(ABSTRACT TRUNCATED AT 250 WORDS)