Inhibition of DNA replicon initiation by 4-nitroquinoline 1-oxide, Adriamycin, and ethyleneimine

Journal Article · Fri Dec 01 04:00:00 EST 1978 · Cancer Res.; (United States)

OSTI ID:5967438

Painter, R B

The effects of three widely differing chemical carcinogens, 4-nitroquinoline 1-oxide, Adriamycin, and ethyleneimine, on DNA replication were studied by pulse labeling of DNA with (/sup 3/H)thymidine and sedimentation analysis with alkaline sucrose gradients. At doses that reduced the rate of DNA synthesis to 30 to 60% of control values, only ethyleneimine produced damage that resulted in lower molecular weights of parental DNA. All three chemicals inhibited replicon initiation, but to differing extents. Inhibition of replicon intitiation was the first clearly identified effect of 4-nitroquinoline 1-oxide and was the main cause of inhibition of DNA synthesis. Ethyleneimine caused severe inhibition of replicon initiation, but blocks to chain elongation also contributed significantly to the inhibition of overall DNA synthesis. Adriamycin affected replicon initiation to a small but significant extent; the primary cause of inhibition of DNA synthesis by this drug was a slowing of the rate of chain elongation. These results indicate that inhibition of replicon initiation is an important mechanism for the action of DNA-damaging agents in mammalian cells and strengthen the concept that control of DNA replication depends on the structural integrity of a chromosomal subunit that consists of several replicons.

• Research Organization: Univ. of California, San Francisco
• OSTI ID: 5967438
• Journal Information: Cancer Res.; (United States), Journal Name: Cancer Res.; (United States) Vol. 38; ISSN CNREA
• Country of Publication: United States
• Language: English

Related Subjects

550200* -- Biochemistry
59 BASIC BIOLOGICAL SCIENCES
AZINES
CARCINOGENS
CELL CULTURES
CELL CYCLE
DNA
DNA REPLICATION
ELONGATION
HELA CELLS
HETEROCYCLIC COMPOUNDS
INHIBITION
LABELLED COMPOUNDS
NUCLEIC ACID REPLICATION
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PYRIMIDINES
RIBOSIDES
THYMIDINE