In vivo and in vitro binding of benzene to nucleic acids and proteins of various rat and mouse organs

Abstract

Benzene binds to macromolecules of various organs in the rat and mouse in vivo. Labelling of RNA and proteins is higher (1 order of magnitude) than DNA labelling, which is low in many organs (liver, spleen, bone marrow and kidney), and negligible in lung; no difference between labelling of rat and mouse organs was found. The covalent binding index (CBI) value was about 10, i.e. typical of genotoxic carcinogens classified as weak initiators. In vitro binding of benzene to nucleic acids and proteins is mediated by hepatic microsomes, but not by microsomes from kidney, spleen and lung, or by cytosol from whatever organ. Nucleic acid binding can be induced by pretreatment with phenobarbitone (PB) and suppressed in the presence of SKF 525-A, of cytosol and/or GSH or of heat-inactivated microsomes. Labelling of exogenous DNA is low and is similar in the presence of rat or mouse microsomes in agreement with the low interaction with DNA measured in vivo.