/sup 32/P-postlabeling assay in mice of transplacental DNA damage induced by the environmental carcinogens safrole, 4-aminobiphenyl, and benzo(a)pyrene

Journal Article · Sun Jun 01 04:00:00 EDT 1986 · Cancer Res.; (United States)

OSTI ID:5487964

Lu, L J; Disher, R M; Reddy, M V; Randerath, K

Transplacental exposure of fetuses to carcinogens is known to induce tumors in the offspring, often with a high incidence and short latency. While covalent adduction of DNA appears to be essential for tumor initiation, little is known about the binding of carcinogens to the DNA of fetal tissues. A sensitive /sup 32/P-postlabeling method enabled us to study the binding of the environmental carcinogens safrole (600 mumol/kg p.o.), 4-aminobiphenyl (800 mumol/kg), and benzo(a)pyrene (200 mumol/kg) to the DNA of various maternal and fetal tissues after administration of test carcinogens to pregnant ICR mice on day 18 of gestation. The results show that these carcinogens bound to the DNA of maternal and fetal liver, lung, kidney, heart, brain, intestine, skin, maternal uterus, and placenta, with organ-specific quantitative and qualitative differences. It was possible for the first time to analyze DNA adduct patterns in minute amounts of tissue, for example those available from fetal heart. The covalent binding index 24 h after safrole treatment was estimated for the different organs and ranged from 0.1 to 247 and 0.1 to 5.8 for maternal and fetal DNA, respectively. Covalent binding index values of 0.2 to 13 and 0.1 to 0.3 for maternal and fetal DNA, respectively, were found for 4-aminobiphenyl. Benzo(a)pyrene treatment yielded covalent binding index values of 0.6 to 6.5 and 0.3 to 0.7 for maternal and fetal DNA, respectively. In both maternal and fetal tissues, safrole exhibited preferential binding to liver DNA. 4-Aminobiphenyl bound preferentially to DNA of maternal liver and kidney but showed no preference among fetal tissues. Benzo(a)pyrene exhibited weak tissue preference in both maternal and fetal organs.

• Research Organization: Baylor College of Medicine, Houston, TX
• OSTI ID: 5487964
• Journal Information: Cancer Res.; (United States), Journal Name: Cancer Res.; (United States) Vol. 6; ISSN CNREA
• Country of Publication: United States
• Language: English

Related Subjects

550501 -- Metabolism-- Tracer Techniques
560305* -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ADDUCTS
ANIMALS
AROMATICS
BENZOPYRENE
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
BIPHENYL
BODY
BRAIN
CARCINOGEN SCREENING
CARCINOGENS
CARDIOVASCULAR SYSTEM
CENTRAL NERVOUS SYSTEM
CONDENSED AROMATICS
COVALENCE
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
DNA
DNA ADDUCTS
FEMALE GENITALS
FETAL MEMBRANES
FETUSES
GASTROINTESTINAL TRACT
GENETIC EFFECTS
GLANDS
HEART
HYDROCARBONS
INTESTINES
ISOTOPE APPLICATIONS
ISOTOPES
KIDNEYS
KINETICS
LIGHT NUCLEI
LIVER
LUNGS
MAMMALS
MEMBRANES
METABOLISM
MICE
NERVOUS SYSTEM
NUCLEI
NUCLEIC ACIDS
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANS
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PLACENTA
PREGNANCY
RADIOISOTOPES
REACTION KINETICS
RESPIRATORY SYSTEM
RODENTS
SCREENING
SKIN
TRACER TECHNIQUES
UTERUS
VERTEBRATES