Embryonic mutation as a possible cause of in utero carcinogenesis in mice revealed by postnatal treatment with 12-O-tetradecanoylphorbol-13-acetate

Journal Article · Sun Apr 01 00:00:00 EST 1990 · Cancer Research; (USA)

OSTI ID:7004350

Nomura, T; Nakajima, H; Hatanaka, T; Kinuta, M; Hongyo, T ^[1]

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1. Osaka Univ. (Japan)

Although in utero irradiation at early stages induced a high incidence of somatic mutations at coat color genes in the embryos of a specified tester strain (PT x HT F1) of mice, it was not carcinogenic by itself. However, in utero-irradiated animals did develop skin tumors and hepatomas (but not leukemias) by the postnatal administration of 12-O-tetradecanoylphorbol-13-acetate. The incidence of both tumors and embryonic mutations increased with in utero doses of X-rays. Furthermore, a large reduction of tumor incidence, about 80%, was observed by low-dose-rate irradiation, similar to the 75% reduction in spot size found for embryonic mutations. The tumor nodule size was also dramatically reduced by low-dose-rate irradiation. Consequently, the induced incidence and size of tumors produced by 12-O-tetradecanoylphorbol-13-acetate treatment parallel those which are observed for coat color mutations as expected, because somatic mutations observed in the pigment cells must similarly occur in embryonic cells of other organs. The larger the clone of mutant cells, the greater their chance of becoming tumorigenic by 12-O-tetradecanoylphorbol-13-acetate posttreatment. These results strongly support the recent epidemiological survey showing that adult types of cancers, but not leukemias, are increasing in the atomic bomb survivors exposed in utero, since humans are continuously exposed to a variety of cancer-promoting agents in contrast to experimental animals reared without such exposures.

• OSTI ID: 7004350
• Journal Information: Cancer Research; (USA), Vol. 50:7; ISSN 0008-5472
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
PHORBOL ESTERS
CARCINOGENESIS
SOMATIC MUTATIONS
RADIOINDUCTION
DOSE-RESPONSE RELATIONSHIPS
EMBRYOS
EXPERIMENTAL NEOPLASMS
GENETIC RADIATION EFFECTS
HEPATOMAS
MICE
PREGNANCY
SKIN
SYNERGISM
X RADIATION
ANIMALS
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
BODY
CARCINOGENS
DISEASES
ELECTROMAGNETIC RADIATION
ESTERS
GENETIC EFFECTS
IONIZING RADIATIONS
MAMMALS
MUTATIONS
NEOPLASMS
ORGANIC COMPOUNDS
ORGANS
PATHOGENESIS
RADIATION EFFECTS
RADIATIONS
RODENTS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology
560152 - Radiation Effects on Animals- Animals