Modulation of the cell cycle of cultured mouse liver cells by benzo(a)pyrene and its derivatives
We have used flow cytometry to monitor the alterations in cell cycle distributions caused by chemical carcinogens. Two closely derived mouse liver cell strains growing in culture have been studied with regard to the effect of benzo(a)pyrene and derivatives of benzo(a)pyrene on DNA synthesis. The derivatives tested were (+-)-trans-7..cap alpha..,8..beta..-dihydroxy-7,8-dihydrobenzo(a)pyrene; (+-)-7..cap alpha..,8..beta..-dihydroxy-9..beta..,10..beta..-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene (diol-epoxide) and 7,8,9,10-tetrahydroxy-7,8,9,10-tetrahydrobenzo(a)pyrene. Flow cytometry analysis and measurements of (/sup 3/H)thymidine incorporation into DNA showed that the diol-epoxide increased the number of cells involved in DNA synthesis but that the rate of DNA synthesis was greatly reduced. Benzo(a)pyrene and +-(trans)-7..cap alpha..,8..beta..-dihydroxy-7,8-dihydrobenzo(a)pyrene had this same effect on NMuLi clone 8 but not on NMuLi clone 7. The perturbations caused by diol-epoxide took place within one cell cycle, and the cell did not traverse a second cycle. Kinetic modeling studies indicated that the cell cycle perturbations caused by diol-epoxide are consistent, with the rate of traverse of S being slower than other phases of the cell cycle, and that as cells move through S their rate of DNA synthesis decreases.
- Research Organization:
- Univ. of California, Berkeley
- OSTI ID:
- 6601469
- Journal Information:
- Cancer Res.; (United States), Journal Name: Cancer Res.; (United States) Vol. 39; ISSN CNREA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
560301* -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
AROMATICS
AZINES
BENZOPYRENE
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMISTRY
BODY
CELL CULTURES
CELL CYCLE
CHEMISTRY
CLONE CELLS
CONDENSED AROMATICS
DIGESTIVE SYSTEM
DISTURBANCES
DNA REPLICATION
EPOXIDES
GLANDS
HETEROCYCLIC COMPOUNDS
HYDROCARBONS
HYDROGEN ISOTOPES
ISOTOPES
LIGHT NUCLEI
LIVER
MAMMALS
METABOLISM
MICE
NUCLEI
NUCLEIC ACID REPLICATION
NUCLEOSIDES
NUCLEOTIDES
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANS
PYRIMIDINES
RADIOISOTOPES
RIBOSIDES
RODENTS
SENSITIVITY
THYMIDINE
TOXICITY
TRITIUM
VERTEBRATES
YEARS LIVING RADIOISOTOPES