Cytologic Effects of Air Force Chemicals
Abstract
Studies of DNA replication and repair in cell cultures have shown that hydrazine, although highly toxic to cells, does not damage DNA and thus interfere directly with DNA replication in Chinese hamster ovary cells grown in vitro, nor does it affect DNA repair synthesis in CCL-185 human lung cells grown in vitro. Hydrazine does not inhibit the methylation of DNA by the direct acting alkylating agent methylmethanesulfonate (MMS) in lungs of mice exposed in vivo, nor does it inhibit the removal of methylated DNA bases. A method has been developed for treating lung slices of rats and mice in vitro with chemicals and monitoring their effect on DNA replication and repair. This method has been used to show that the alkylating agents MMS and 4-nitroquinoline-1-oxide (4NQO), both mutagens and carcinogens, induce DNA repair in both rat and mouse lung tissue after in vitro exposure. Mice were injected with naphtalene and bromobenzene and elevated levels of DNA replication and repair were observed in lung slices tested in vitro. This may be the result of sensitive cells in the lung being killed by the chemicals and the survivors replicating with an increased capacity for repair while they were proliferating. In a comparable experiment, treatment of mice with hydrazine was found to only marginally increase lung cell replication. Peripheral lymphocytes from human blood were exposed to carcinogens in vitro and DNA repair synthesis was measured. Exposure to 4NQO, MMS, nitrogen mustard or MMC, all known DNA damaging agents (although each with a different mode of action), induced DNA repair activity. This repair activity was greatly amplified when lymphocytes were stimulated to divide with phytohemagglutinin.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 1980
- Accession Number
- ADA092752
Entities
People
- Ronald E. Rasmussen
Organizations
- University of California, Irvine