Inhibition of DNA replication and repair by anthralin or danthron in cultured human cells

Journal Article · Thu Jul 01 04:00:00 EDT 1982 · J. Invest. Dermatol.; (United States)

DOI:https://doi.org/10.1111/1523-1747.ep12510431· OSTI ID:6702955

Clark, J M; Hanawalt, P C

The comparative effects of the tumor promoter anthralin and its analog, danthron, on semiconservative DNA replication and DNA repair synthesis were studied in cultured human cells. Bromodeoxyuridine was used as density label together with /sup 3/H-thymidine to distinguish replication from repair synthesis in isopycnic CsCl gradients. Anthralin at 1.1 microgram inhibited replication in T98G cells by 50%. In cells treated with 0.4 or 1.3 microM anthralin and additive effect was observed on the inhibition of replication by ultraviolet light (254 nm). In cells irradiated with 20 J/m2, 2.3 microM anthralin was required to inhibit repair synthesis by 50%. Thus there was no selective inhibitory effect of anthralin on repair synthesis. Danthron exhibited no detectable effect on either semiconservative replication or repair synthesis at concentrations below about 5.0 microM. Neither compound stimulated repair synthesis in the absence of ultraviolet irradiation. Thus, anthralin and danthron do not appear to react with DNA to form adducts that are subject to excision repair. Although both compounds appear to intercalate into supercoiled DNA in vitro to a limited extent, the degree of unwinding introduced by the respective drugs does not correlate with their relative effects on DNA synthesis in vivo. Therefore the inhibitory effect of anthralin on DNA replication and repair synthesis in T98G cells does not appear to result from the direct interaction of the drug with DNA.

• Research Organization: Department of Biological Sciences, Stanford University, California
• OSTI ID: 6702955
• Journal Information: J. Invest. Dermatol.; (United States), Journal Name: J. Invest. Dermatol.; (United States) Vol. 79:1; ISSN JIDEA
• Country of Publication: United States
• Language: English

Related Subjects

550201 -- Biochemistry-- Tracer Techniques
550401 -- Genetics-- Tracer Techniques
560301* -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
BIOLOGICAL EFFECTS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
CELL CULTURES
COMPARATIVE EVALUATIONS
DNA
ELECTROMAGNETIC RADIATION
ELECTROPHORESIS
GENETIC EFFECTS
IN VITRO
LABELLED COMPOUNDS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
PROMOTERS
QUANTITY RATIO
RADIATIONS
RECOVERY
REPAIR
TRITIUM COMPOUNDS
TUMOR PROMOTERS
ULTRAVIOLET RADIATION