Dose dependency of aflatoxin B/sub 1/ binding on human high molecular weight DNA in the activation of proto-oncogene
The binding of aflatoxin B/sub 1/, AFB/sub 1/, a potent hepatocarcinogen, to various high molecular weight (HMW) DNAs from human normal liver and two liver cancer cell lines, Alexander primary liver carcinoma (PLC) and Mahlavu hepatocellular carcinoma (hHC) and from NIH/3T3 cell have been investigated. The kinetics of AFB/sub 1/ binding to these DNAs showed similar initial rates but the extents of binding to the PLC and hHC DNAs seemed to be slightly higher. Preferential AFB/sub 1/ bindings were identified in both PLC and hHC DNAs compared to normal liver DNA. A critical AFB/sub 1/ binding dosage, ranging 100 to 460 fmole/..mu..g DNA, was found to activate the carcinogenic effect of the Mahlavu hHC HMW DNA, but not normal liver HMW DNA, rendering it capable of inducting focal transformation in NIH/3T3 cell. Excessive AFB/sub 1/ binding on the hHC and PLC HMW DNAs resulted in an over-kill of both cell transformation capability and templating activity of the DNA.
- Research Organization:
- National Cancer Institute, Bethesda, MD
- OSTI ID:
- 5387994
- Journal Information:
- Environ. Health Perspect.; (United States), Vol. 62
- Country of Publication:
- United States
- Language:
- English
Similar Records
Activation of the H-ras oncogene in hepatocellular carcinomas initiated with diethylnitrosamine and promoted by a dietary methyl deficiency
Characterization of c-Ki-ras oncogene alleles by direct sequencing of enzymatically amplified DNA from carcinogen-induced tumors
Related Subjects
AFLATOXIN
CONFIGURATION INTERACTION
DNA
TRITIUM COMPOUNDS
CARCINOMAS
LIVER
METABOLIC ACTIVATION
TUMOR CELLS
ANIMAL CELLS
ANTIGENS
BODY
DIGESTIVE SYSTEM
DISEASES
GLANDS
LABELLED COMPOUNDS
MATERIALS
NEOPLASMS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANS
TOXIC MATERIALS
TOXINS
560301* - Chemicals Metabolism & Toxicology- Cells- (-1987)