Js. Tuo et al., Enhanced benzene-induced DNA damage in PMA-stimulated cells in vitro and in LPS-treated animals, FREE RAD B, 26(7-8), 1999, pp. 801-808
The present study investigated the interaction between inflammatory reactio
ns and benzene in vitro and in vivo with respect to oxidative DNA damage. I
n the in vitro models the oxidative burst of cells was induced by the pretr
eatment with phorbol myristate acetate (PMA) and in the in vivo models of i
nflammation mice were pretreated with lipopolysaccharide (LPS). The oxidati
ve DNA damage was indicated by 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG
) and strand breaks as assessed by alkaline single cell gel electrophoresis
(SCGE, Comet assay). The results showed that combination of PMA and benzen
e enhanced the level of 8-oxodG in DNA from mouse bone marrow cells by 197%
, from human lymphocytes by 188% and from human neutrophils by 205% (p < .0
5). Pretreatment of mice with LPS and benzene resulted in an enhanced Comet
score formation in bone marrow cells by 98% and in lymphocytes by 39% in C
omet score (p < .05) and in an enhanced 8-oxodG level in bone marrow cells
by 290%. The effects of the combined treatment with PMA/LPS and benzene exc
eeded the sum of the effects induced by PMA/LPS or benzene alone. The produ
ction of nitrate/nitrite showed a two fold increase in the supernatant from
incubation of benzene and PMA-pretreated neutrophils. The increase in the
8-oxodG level in the human neutrophil incubation system demonstrated a corr
elation with nitrate/nitrite production, indicating a possible relationship
with the generation of reactive nitrogen species. (C) 1999 Elsevier Scienc
e Inc.