Lymphotoxin prevention of diethylnitrosamine carcinogenesis in vivo

Journal Article · Wed Sep 01 04:00:00 EDT 1982 · J. Natl. Cancer Inst.; (United States)

OSTI ID:6708035

Ransom, J H; Evans, C H; DiPaolo, J A

Development of intervention measures to control cancer would be facilitated by being able to monitor in vivo carcinogenesis by in vitro quantitation of early indices of neoplastic transformation to assess the in vivo effectiveness of preventive-therapeutic measures. Pregnant Syrian golden hamsters were used in an in vivo-in vitro transplacental model of carcinogenesis to determine the extent that in vivo administration of immunologic hormone preparations along with chemical carcinogen would prevent morphologic transformation assessed in vitro. Pregnant hamsters at 10-11 days of gestation were given injections ip of 3 mg diethylnitrosamine (DENA)/100 g body weight and were killed 2 days later when fetal cells were seeded for colony formation. The frequency of morphologically transformed colonies was assessed after 7 days of growth. Cloning efficiency and mean transformation frequency after DENA exposure were 3.6% and 1 X 10(-4) per cell seeded, respectively. The ip injection of an immunologic hormone preparation reduced the transformation frequency by 46%. The hormone preparation, containing 10,000 U of lymphotoxin but no detectable interferon, was the ultrafiltered lymphokines (greater than 10,000 mol wt) from phytohemagglutinin-stimulated hamster peritoneal leukocytes. The effect of lymphotoxin on cocarcinogenic exposure of fetal cells to DENA in vivo followed by X-irradiation in vitro was also determined. Cells exposed to 250 rad in vitro had a cloning efficiency of 0.5% and a transformation frequency of 0.4 X 10(-4) per cell seeded. After DENA injection and X-irradiation, the transformation frequency increased to 1 X 10(-4) and was inhibited 64% by lymphotoxin in vivo. Thus immunologic hormones (e.g., lymphotoxin) can prevent carcinogenesis in vivo. Furthermore, in vitro quantitation of transformation is a rapid means for evaluating therapeutic and autochthonous effector mechanisms for their ability to prevent or otherwise modulate carcinogenesis in vivo.

• Research Organization: Division of Cancer Cause and Prevention, National Cancer Institute, U.S. Department of Health and Human Services, Bethesda, MD
• OSTI ID: 6708035
• Journal Information: J. Natl. Cancer Inst.; (United States), Journal Name: J. Natl. Cancer Inst.; (United States) Vol. 69:3; ISSN JNCIA
• Country of Publication: United States
• Language: English

Related Subjects

560152* -- Radiation Effects on Animals-- Animals
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
BIOLOGICAL EFFECTS
BIOLOGICAL PATHWAYS
BIOLOGICAL RADIATION EFFECTS
CARCINOGENESIS
CARCINOGENS
ELECTROMAGNETIC RADIATION
HAMSTERS
IMMUNE REACTIONS
IMMUNE SERUMS
IMMUNITY
IN VIVO
IONIZING RADIATIONS
MAMMALS
ONCOGENIC TRANSFORMATIONS
PATHOGENESIS
PREGNANCY
RADIATION EFFECTS
RADIATIONS
RADIOSENSITIVITY EFFECTS
RODENTS
VERTEBRATES
X RADIATION