Comparative changes in rat liver cytosolic proteins by mirex, diethylnitrosamine, and dimethylnitrosamine exposure

Using a newborn rat model for carcinogenesis, changes in liver cytosolic proteins at three stages of tumorigenesis, on Days 21, 97, and 120, by mirex (dodecachloropentacyclo-1,3,4-metheno-2H-cyclobuta[cd] pentalene), and diethyl- and dimethylnitrosamines (DEN and DMN) were studied. Following multiple exposure to the hepatocarcinogens, groups of weanling rats were given dietary phenobarbital (PB) up to 120 days. SDS-PAGE separation of cytosolic proteins showed that at 21 days, prior to PB, two proteins of 26K and 23K mol wt were significantly induced by mirex and DMN while a high mol wt 63K protein was induced only by DEN and DMN. During the period of PB treatment up to 97 days, these proteins were well sustained at a higher level. A marked increase in 21K protein band was also observed at this point. In tumor tissues obtained from DEN and DMN rats continued on PB diet for 120 days, the high level of 63K protein was seen only in DEN and not in DMN tumor. The tumors also showed a significant reduction in 25K protein compared to 21- and 97-day groups. The presence of even lower mol wt proteins of 14-21K was seen in tumors. The early detection and further characterization of these low mol wt proteins may provide clues as to whether they are preneoplastic markers or oncogene products as speculated by other investigators. Moreover, certain similarities in the induction of cytosolic proteins by "epigenetic" and "genotoxic" carcinogens raise more interesting questions regarding the mechanisms of action of these distinct classes of carcinogens.