The absence of complete inhibition of SSB formation by the hydroxyl radical scavenger mannitol may derive from the fact that much higher levels of amino acids, vitamins, and other potential targets for oxygen radicals are already abundant in the assay medium and would compete with the mannitol.If these compounds mediate DNA damage whereas mannitol does not, then much higher levels of mannitol than those employed herein would be required to inhibit damage in these assays.Moreover, HO is only one of many primary and secondary reactive oxygen intermediates, such as chloramines and aldehydes also concluded that the level of thymine base changes formed in NIHT cells exposed to activated macrophages did not correlate strictly with the producing capacity of the macrophages.Further experiments will be required to verify this hypothesis.Pristaneelicited peritoneal macrophages did not cause any detectable DNA damage in neighboring tumor cells when tested up to a ratio of: macrophage fraction cells:target cell.It is possible that these results may have derived from the design of the experiments and that the macrophages need to be adherent in order to elaborate their maximal oxidative burst activity.Alternatively, pristaneelicited macrophages may require some form of synergism with other cells types in order to produce clastogenic compounds.Nonetheless, the data are consistent with previous studies showing that paraffin oilelicited murine macrophages are only minimally cytocidal and produce only nmol O min cells and nmol HO minlO cells when tested in adherent culture. Hence, although paraffin oilelicited macrophages are more highly activated than thioglycollateelicited macrophages, their potential contribution to the DNA damage that may be occurring in the pristaneprimed peritoneal cavity has yet to be fully elucidated.However, the apparent discrepancy may be explained by several significant distinctions between the two kinds of studies.That is, the experiments, in which indomethacin has had no effect or has enhanced damage have involved short term assays for relatively large levels of DNA damage whereas experiments in which indomethacin has been inhibitory have employed highly sensitive assays for measuring low levels of residua chromosomal aberrations found several days after induction of damage. Hence, although indomethacin does not inhibit formation of gross SSB in a target cell, it may prevent formation, persistence, or conversion of a particular form of DNA modification that leads to a lasting chromosomal aberration.This point may be especially important in light of the fact that administration of indomethacin to pristaneprimed mice dramatically reduces the incidence of plasma cell tumorigenesis by an as yet unknown mechanism.These tumors develop histologically in the fixed oil granulomatous tissue from B cellsplasma cells that home into the chronic inflammatory tissue.Pristane induces a sustained influx of neutrophils into the peritoneal space and into the fixed oil granuloma. Evidence for hypochlorous acid generation.Their physiological adaptive nature.Nature. Carcinogenesis. Sdence. Carcinogenesis. Received on July; revised on September; accepted on September, Downloadedfromhttp: carcin. oxfordjournals. org atPennsylvani a State UniversityonM arch, However, exposure to high concentrations of oxygen is known to induce damage to cells, possibly due to an increased oxygen radical production.Oxidative DNA base modifications were determined by converting oxidized DNA bases to strand breaks using bacteria formamidopyrimidineDNA glycosylase, a DNA repair enzyme, which specifically nicks DNA at sites of oxoguanines and formamidopyrimidines.