Similarities between the biochemical actions of cycasin and dimethylnitrosamine

Abstract

Rats were given the hepatotoxin and carcinogen cycasin [from Cycas circinalis] by stomach tube. In one experiment, rats whose RNA was previously labelled with [14C]-formate were given the acetate ester of the aglycone form of cycasin, methylazoxymethanol, by intraperitoneal injection. Incorporation of 14C from L-[U-14C]leucine into the proteins of some organs was measured in cycasin-treated rats. Cycasin inhibited leucine incorporation into liver proteins but not into kidney, spleen or ileum proteins. This inhibition was not evident until about 5 hr. after cycasin administration, but once established it persisted for the next 20 hr. Methylation of nucleic acids was detected in some organs of rats treated with cycasin or methylazoxymethanol. The purine bases of RNA and DNA were isolated by acid hydrolysis followed by ion-exchange column chromatography. The resulting chromatograms showed an additional purine base that was identified as 7-methylguanine. In animals treated with the toxin, liver RNA was methylated to a greater extent than was either kidney or small-intestine RNA. Also, as a result of cycasin administration, liver DNA guanine was methylated to a greater extent than was RNA guanine. These results are discussed in relation to comparable experiments with dimethylnitrosamine. Cycasin and dimethylnitrosamine are metabolized to the same biochemically active compound, perhaps diazomethane, but various tissues differ in their capacity to metabolize the 2 carcinogens.