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We have proposed that transformation of cells to tumorigenicity by chemical carcinogens can depend upon stabilization of a protein responsible for growth regulation. Cell kinetic experiments in which normal and benzo[a]pyrene-transformed BALB/c-3T3 cells were pulsed with cycloheximide indicated this protein should have a half-life of a few hours in normal(More)
The chemical stability of aflatoxin B1 bound to calf thymus DNA was studied over a 48-hour exposure to phosphate buffers at pH 6.8-8.0 (37 degrees C). During this time, aliquots of the aflatoxin B1-modified DNA were acid-hydrolyzed and analyzed for the presence of 2,3-dihydro-2-(N7-guanyl)-3-hydroxyflatoxin B1, 2,3-dihydro-2,3-dihydroxy-aflatoxin B1, and(More)
Primary cell cultures derived from human skin epithelium metabolized benzo(a)pyrene to three classes of compounds: phenols, quinones, and dihydrodiols. The relative proportions of metabolites varied according to the skin donor but differed from the pattern of metabolites in rat liver microsome preparations. While appreciable amounts of 7,8- and(More)
Differences in benzo(a)pyrene metabolite pattern have been shown by rodent liver microsomes (Sprague-Dawley) and rodent embryo cells from Syrian hamsters and NIH Swiss mice. Rodent liver induced by methylcholanthrene shows marked quantitative variation between species. Additional pattern changes were found in mouse and hamster embryo secondary cultures with(More)
The covalent binding of the hepatocarcinogen aflatoxin B1 by rat liver microsomes to calf thymus DNA resulted in a binding level equal to one aflatoxin residue per 60 DNA nucleotides. An aflatoxin derivative-guanine adduct was efficiently liberated from DNA with formic acid. Analytical reversed-phase high-pressure liquid chromatography of the DNA(More)
Exposure to genotoxic chemicals at a young age increases cancer incidence later in life. Aflatoxin B(1) (AFB(1)) is a potent genotoxin that induces hepatocellular carcinoma (HCC) in many animal species and in humans. Whereas adult mice are insensitive to aflatoxin-induced carcinogenesis, mice treated with AFB(1) shortly after birth develop a high incidence(More)
We examined patterns of covalent modifications of DNA produced in rat liver after exposure to single and multiple doses of aflatoxin B1. The principal product, previously identified as 2,3-dihydro-3-hydroxy(N7-guanyl) aflatoxin B1, was removed rapidly from liver DNA in vivo after a 0.6-mg/kg dose was administered i.p. to male Fischer rats. This lesion had(More)
The covalent interactions between aflatoxin B1 (AFB1) and DNA were investigated in the inbred F344 rat and noninbred CD -1 Swiss mouse. A good correlation was found between the level of covalent modification of DNA, species sensitivity, and organ specificity, to the toxic effects of AFB1. The patterns of AFB1 acid hydrolysis products from DNA isolated from(More)
The products of in vivo covalent binding of activated aflatoxin B1 (AFB1) to DNA have been investigated in rats. The principal covalent product formed in liver DNA of rats treated with AFB1 has been identified as 2,3-dihydro-2-(N7-guanyl)-3-hydroxy-aflatoxin B1. This compound was isolated from the liver DNA of rats dosed with AFB1 (2.0 mg/kg) in sufficient(More)