Induction of unscheduled DNA synthesis in primary cultures of rat pancreatic cells following in vivo and in vitro treatment with genotoxic agents

Journal Article · Sun Jan 01 04:00:00 EST 1984 · Environ. Mutagen.; (United States)

DOI:https://doi.org/10.1002/em.2860060308· OSTI ID:6593949

Steinmetz, K L; Mirsalis, J C

The pancreas is a key target tissue in human and animal carcinogenesis, yet few short-term test systems measure genotoxicity in pancreatic cells. A method has been developed for the measurement of DNA repair as unscheduled DNA synthesis (UDS) in primary cultures of rat pancreatic cells (PRP) following in vitro or in vivo exposures to chemicals. PRP were isolated from female Sprague-Dawley (SD) or male Fischer-344 rats by mincing the pancreas in a collagenase solution followed by digestion in dispase. For vitro exposures, PRP were incubated with /sup 3/H-thymidine (/sup 3/H-TdR) in the presence of genotoxic agents for 18-22 hr. For in vivo exposures, male Fischer-344 rats were treated with genotoxic agents 2 hr prior to sacrifice of the animals, and cells were incubated with /sup 3/H-TdR. Cells isolated from female SD rats and treated in vitro with methylmethane sulfonate (MMS), ethylmethane sulfonate (EMS), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), and the pancreatic carcinogen azaserine all showed UDS. Cells treated in vitro with the hepatocarcinogens 2-acetylaminofluorene (2-AAF) and dimethylnitrosamine (DMN) and with the multisite carcinogen benzo(a) pyrene (B(a)P) yielded no UDS. In vivo treatment with MMS at 100 mg/kg and with azaserine at 100 mg/kg yielded varying degrees of UDS.

• Research Organization: SRI International, Menlo Park, CA
• OSTI ID: 6593949
• Journal Information: Environ. Mutagen.; (United States), Journal Name: Environ. Mutagen.; (United States) Vol. 6:3; ISSN ENMUD
• Country of Publication: United States
• Language: English

Related Subjects

560301 -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
560305* -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMINES
ANIMAL CELLS
ANIMALS
AROMATICS
AUTORADIOGRAPHY
AZINES
BENZOPYRENE
BIOLOGICAL EFFECTS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
BIOSYNTHESIS
BODY
CONDENSED AROMATICS
DIGESTIVE SYSTEM
DNA
EMS
ENDOCRINE GLANDS
ESTERS
GLANDS
HETEROCYCLIC COMPOUNDS
HYDROCARBONS
IN VITRO
IN VIVO
LABELLED COMPOUNDS
MAMMALS
METHYL METHANESULFONATE
MUTAGENS
NITROSAMINES
NITROSO COMPOUNDS
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
PANCREAS
PYRIMIDINES
RATS
RECOVERY
REPAIR
RIBOSIDES
RODENTS
SULFONIC ACID ESTERS
SYNTHESIS
THYMIDINE
TRITIUM COMPOUNDS
VERTEBRATES