Effect of carcinogen release rate on the incidence of preneoplastic and neoplastic lesions of the respiratory tract epithelium in rats

Journal Article · Mon Nov 01 00:00:00 EST 1982 · JNCI, J. Natl. Cancer Inst.; (United States)

OSTI ID:5345474

Shiba, M ^[1]; Klein-Szanto, A J.P.; Marchok, A C; Pal, B C; Nettesheim, P

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1. Univ. of Tennessee, Oak Ridge

Inbred F344 rat tracheal transplants were exposed to 7,12-dimethylbenz(a)anthracene (DMBA) delivered at different release rates from intraluminal pellets made of various matrices to study the effect of carcinogen dose rate on the induction of lesions in the epithelium. These matrices were beeswax, beeswax-stearyl alcohol, and beeswax-cholesterol. In addition, DMBA adsorbed onto carbon particles was dispersed in beeswax-stearyl alcohol. The fastest release was obtained from beeswax pellets from which 99% of the carcinogen (198 ..mu..g) was released in 4 weeks, and the slowest release was from DMBA adsorbed on carbon at a ratio of 1:9 from which only 56% (113 ..mu..g) was released in 16 weeks. Morphometry of histologic sections showed marked differences in the percentage of luminal surface covered by dysplastic-neoplastic epithelium (i.e., 7.5% in the tracheas exposed to the fastest releasing pellets and 46.3% in the tracheas exposed to the slowest releasing pellets). An inverse linear correlation was found between the cumulative amount of DMBA release from the different pellet matrices at 2 weeks and the incidence of dysplastic plus neoplastic lesions of tracheal epithelium at 16 weeks. The results indicated that lower doses of carcinogen delivered slowly are more effective in producing dysplastic plus neoplastic lesions than higher doses delivered rapidly.

• DOE Contract Number: W-7405-ENG-26
• OSTI ID: 5345474
• Journal Information: JNCI, J. Natl. Cancer Inst.; (United States), Vol. 69:5
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
DIMETHYLBENZANTHRACENE
BIOLOGICAL EFFECTS
TRACHEA
ONCOGENIC TRANSFORMATIONS
ALCOHOLS
CARBON
CARCINOGENS
CHOLESTEROL
DOSE RATES
DOSE-RESPONSE RELATIONSHIPS
EPITHELIUM
RATS
TRANSPLANTS
WAXES
ANIMAL TISSUES
ANIMALS
AROMATICS
BODY
CONDENSED AROMATICS
ELEMENTS
HYDROXY COMPOUNDS
MAMMALS
NONMETALS
ORGANIC COMPOUNDS
OTHER ORGANIC COMPOUNDS
RESPIRATORY SYSTEM
RODENTS
STEROIDS
STEROLS
TISSUES
VERTEBRATES
560306* - Chemicals Metabolism & Toxicology- Man- (-1987)