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Lack of I-compounds in DNA from a spectrum of Morris hepatomas
K Randerath1, E Randerath, T F Danna
1Department of Pharmacology, Baylor College of Medicine, Houston, TX 77030.
Abstract:
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 x 10(8) 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.
Insights
Indigenous DNA modifications, known as I-compounds, are significantly deficient in rat hepatomas. This deficiency suggests I-compounds may play a role in preventing or maintaining cancerous liver neoplasms.
Area of Science:
- Biochemistry
- Molecular Biology
- Toxicology
Background:
- A progressive loss of I-compounds (age-dependent, putative indigenous DNA modifications) has been observed during chemically induced hepatocarcinogenesis in rats.
- I-compounds exhibit significant tissue-, sex-, strain-, and species-specificity.
Purpose of the Study:
- To investigate the status of I-compounds in hepatic neoplasms (Morris hepatomas).
- To determine if I-compound deficiency correlates with tumor growth rate.
Main Methods:
- Quantification of I-compounds using the 32P-postlabeling assay.
- Analysis of eight transplantable rat (Morris) hepatomas and host liver samples.
Main Results:
- Most I-compounds detected in normal liver were absent or present at significantly lower levels in hepatomas.
- Hepatomas showed I-compound levels 7-16 times lower than host liver.
- No correlation was found between I-compound deficiency and tumor growth rate.
Conclusions:
- I-compounds are likely normal DNA modifications.
- The deficiency of I-compounds may contribute to the development and maintenance of liver cancer (hepatoma).