DNA replication and unscheduled DNA synthesis in lungs of mice exposed to cigarette smoke
Mice of the hybrid strain BC3F1/Cum (C57BL/Cum X C3H/AnfCum) were chronically exposed to measured amounts of machine-generated whole Kentucky reference 2A1 cigarette smoke. DNA replication and unscheduled DNA synthesis (UDS) were measured in lung tissue in vitro using a short-term organ culture method. Within one week of beginning smoke exposure, DNA replicative activity, as indicated by incorporation of (3H)-thymidine into total lung DNA, was increased more than two-fold over sham-exposed controls and remained elevated as long as smoke exposure was continued. Treatment of lung tissues in vitro with either the lung carcinogen 4-nitroquinoline-1-oxide or methylmethane sulfonate stimulated UDS, measured as incorporation of (3H)thymidine into lung DNA in the presence of hydroxyurea, presumably as the result of DNA repair activity. Until the 10th to 12th week of smoke exposure, at which time the accumulated deposition of total particulate material in the lung was approximately 40 mg, the level of UDS stimulated by the alkylating chemicals declined to approximately 50% of that seen in lung tissue from sham-exposed control mice. If the mice were removed from smoke exposure, DNA replicative activity returned to normal levels within one week, but the UDS response to DNA damage remained depressed up to five months after ending smoke exposure. The results show that both transient and apparently permanent changes are produced in mouse lung as the result of exposure to cigarette smoke. The role of these changes in lung neoplasia is under investigation.
- OSTI ID:
- 5657200
- Journal Information:
- Cancer Res.; (United States), Vol. 41:7
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
DNA
BIOLOGICAL REPAIR
METHYL METHANESULFONATE
BIOLOGICAL EFFECTS
TOBACCO SMOKES
CELL CULTURES
DNA REPLICATION
LUNGS
MICE
TRITIUM COMPOUNDS
AEROSOLS
ANIMALS
BIOLOGICAL RECOVERY
BODY
COLLOIDS
DISPERSIONS
ESTERS
LABELLED COMPOUNDS
MAMMALS
MUTAGENS
NUCLEIC ACID REPLICATION
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
RECOVERY
REPAIR
RESIDUES
RESPIRATORY SYSTEM
RODENTS
SMOKES
SOLS
SULFONIC ACID ESTERS
VERTEBRATES
560305* - Chemicals Metabolism & Toxicology- Vertebrates- (-1987)
550201 - Biochemistry- Tracer Techniques