LACK OF I-COMPOUNDS IN DNA FROM A SPECTRUM OF MORRIS HEPATOMAS

A partial, progressive loss of I-compounds (age-dependent, putative indigenous DNA modifications) has been observed recently during hepatocarcinogenesis induced in rats by 2,3,7,8-tetrachlorodibenzo-p-dioxin, choline-devoid diet or peroxisome proliferators. It was of interest, therefore, to investigate the status of I-compounds in hepatic neoplasms. I-compounds were measured by 32P-postlabeling in eight transplantable rat (Morris) hepatomas of different growth rates and in host liver. Most I-compounds seen in liver were not detected in any of the hepatomas, and those present exhibited low levels. Hepatomas displayed an overall level of one I-compound in 2 × 108 DNA nucleotides, which was 7-16 times lower than liver values. The extent of I-compound deficiency did not correlate with tumor growth rate. These results, taken together with previously documented pronounced tissue-, sex-, strain- and species-specificity of I-compound profiles, suggest that I-compounds are normal DNA modifications and that their deficiency may contribute to development and maintenance of neoplasia. © 1990 Oxford University Press.