Search PubMed⌕ Search

Biomedical subjects

P Amstad

Publications and source records attributed to P Amstad.

38 records · Page 3Linked to original sources
PubMed1984

Evidence for membrane-mediated chromosomal damage by aflatoxin B1 in human lymphocytes.

The hepatocarcinogen aflatoxin B1 (AFB1) was found to be a potent clastogen for phytohemagglutinin stimulated human lymphocytes. It also induced sister chromatid exchanges. These types of chromosomal damage were induced at very low levels of covalent AFB1 - DNA adducts suggesting that AFB1 operates in part by indirect action because of its membrane-active character. The membrane-active character of AFB1 is documented by the following results: (i) AFB1 stimulated the excretion of hydroxy- and/or hydroperoxy-arachidonic acid (AA) and free AA into the culture medium; (ii) the phospholipase A2 inhibitor p-bromophenacylbromide was anticlastogenic ; (iii) the inhibitors of the oxidative metabolism of AA indomethacin, flufenamic acid, 5,8,11,14-eicosatetraynoic acid, nordihydroguaiaretic acid and BN 1015 were anticlastogenic . These results are compatible with the induction of DNA damage by indirect action or the formation of covalent adducts via metabolic activation by cooxygenation . The observation that CuZn superoxide dismutase was anticlastogenic indicates the intermediacy of superoxide in DNA damage formation and supports the former mechanism.

Aflatoxin B1↗
PubMed1983

DNA binding of aflatoxin B1 by co-oxygenation in mouse embryo fibroblasts C3H/10T1/2.

The mechanism of activation of aflatoxin B1 to ultimate metabolites capable of DNA binding was investigated in mouse embryo fibroblasts C3H/10T1/2. The contribution of co-oxygenation reactions which are coupled to arachidonic acid metabolism was assessed by the use of inhibitors of prostaglandin endoperoxide synthetase and lipoxygenase. Indomethacin and 5,8,11,14-icosatetraynoic acid inhibited AFB1-binding to maximally 60%. The antioxidant glutathione was also inhibitory while CuZn superoxide dismutase had no effect or slightly stimulated binding at high concentrations. These results indicate that co-oxygenation plays a major role in AFB1-metabolism in 10T1/2 cells. The observation that the phospholipase A2 inhibitor p-bromophenacylbromide diminished AFB1-DNA binding supports the notion that AFB1, because it is membrane-active, may enhance its own co-oxidative metabolism by stimulating the arachidonic acid cascade.

Aflatoxin B1↗