Involvement of active oxygen species in protein and oligonucleotide degradation induced by nitrofurans

Abstract

It is of great interest to know how nitrofurans are mutagenic and clastogenic. In particular, the 3-amino-2-oxazolidone (AOZ) ring, deriving from a cleavage of furazolidone, is not further metabolized and has been found to be part of protein-bound residues in edible tissues of farm animals and these might be released in the stomach of the consumer. The data in this paper show that isoniazide as well as AOZ and 3-amino-5-morpholinomethyl-2-oxazolidinone (AMOZ), the latter deriving from furaltadone, cause irreversible damage to the prosthetic group of enzymes as well as degrade their polypeptide chain and cause fragmentation of the backbone chain of cellular or isolated DNA and RNA. Cellular DNA was degraded into small fragments of 2000 Mb, while rRNA was completely destroyed. Nitrofuran derivatives and hydrazides, in fact, share an N–N moiety, which is assumed to play an essential role in the irreversible damage observed. The key to the molecular mechanisms by which these compounds cause their irreversible effects may lie in oxygen consumption and electron spin resonance measurements, which reveal that both nitrofurans and isoniazide produce oxygen radicals at various degrees of efficiency. AOZ and AMOZ are not metabolized into more reactive metabolites, being themselves able to react with atmospheric oxygen and induce protein and oligonucleotide damage. The reaction does not require metal ions, although their presence will accelerate it.Key words: nitrofurans, active oxygen, furazolidone, DNA degradation, protein fragmentation.