Ortho-quinones of benzene and estrogens induce hyperproliferation of human peripheral blood mononuclear cells.
Benzene is a known leukemogen. It has been hypothesized that benzene and natural estrogens initiate cancer by forming ortho-quinones (catechol quinones) that react with DNA in cells. These quinones form depurinating DNA adducts that generate the mutations leading to cancer. This study examined whether the treatment of normal human peripheral blood mononuclear cells with the ortho-quinones of benzene or estradiol would form DNA adducts and elicit an alteration in the proliferation of these cells. Both estradiol-3,4-quinone and benzene ortho-quinone formed depurinating DNA adducts and significantly increased the mitogen-induced proliferation of normal blood mononuclear cells. Immunophenotyping of the estradiol-3,4-quinone-treated blood cells indicated that monocyte/macrophage, natural killer and T-cells were particularly prone to hyperproliferation. Thus, DNA damage induced by the ortho-quinones of benzene and estradiol may promote the growth of human blood mononuclear cells, including those that appear in large numbers in leukemia and lymphoma.
Chakravarti
Dhrubajyoti
D
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Zahid
Muhammad
M
Backora
Matthew
M
Myers
Erin M
EM
Gaikwad
Nilesh
N
Weisenburger
Dennis D
DD
Cavalieri
Ercole L
EL
Rogan
Eleanor G
EG
Joshi
Shantaram S
SS
D001554:Benzene / Q000737:chemistry*; D049109:Cell Proliferation; D004247:DNA / Q000378:metabolism; D018736:DNA Adducts / Q000737:chemistry; D004958:Estradiol / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D004967:Estrogens / Q000737:chemistry*; D006801:Humans; D016130:Immunophenotyping / Q000379:methods; D007963:Leukocytes, Mononuclear / Q000166:cytology*; D008956:Models, Chemical; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy; D011809:Quinones / Q000494:pharmacology*; D013997:Time Factors
D018736:DNA Adducts; D004967:Estrogens; D011809:Quinones; C500988:estradiol-3,4-quinone; D004958:Estradiol; D004247:DNA; D001554:Benzene