Carcinogen induced unscheduled DNA synthesis in mouse hepatocytes.

Published

Journal Article

Mouse primary liver cell cultures were examined for evidence of unscheduled DNA synthesis (UDS) following treatment with the carcinogens; dimethylnitrosamine (DMNA), diethylnitrosamine (DENA), 2-acetylaminofluorene (2-AAF), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), benzo(a)pyrene (BP), dimethylbenzanthracene (DMBA), 1,1,-bis(p-chlorophenyl)-2,2,2-trichloroethane (DDT), safrole, diethylstilbestrol (DES), aflatoxin B1 (AFB1), and dieldrin and the noncarcinogens; dimethylformamide (DMF), fluorene, and pyrene. Mouse hepatocyte cultures were simultaneously treated with three concentrations of each compound and 3H-thymidine. After 24 hrs, cells were fixed and processed for autoradiography. 3H-thymidine incorporation in both experimental and control cell nuclei, as evidenced by autoradiographic grains, was quantitated microscopically. DMNA, DENA, 2-AAF, MNNG, BP, AFB1 and DMBA significantly increased UDS over untreated cells at all concentrations studied. DDT, DMF, fluorene, pyrene, safrole, DES, and dieldrin were negative for UDS in all concentrations examined. DMNA, 2-AAF and MNNG were also studied for UDS induction in 2 hr old, 1 day old and 4 day old cultures. A progressive decrease in UDS with increased time after plating was found in DMNA and 2-AAF treated cultures. After 4 days DMNA and 2-AAF induced UDS only at the highest concentrations examined (10(-3) M and 10(-4) M respectively). MNNG induced UDS at all time periods and concentrations sampled. An attempt to enhance the sensitivity of the UDS assay by inducing the mixed function oxidative enzyme activity in the hepatocytes with phenobarbital administered in vivo resulted in no statistically significant increase in UDS with DMNA, 2-AAF, MNNG, DDT, and dieldrin when compared with cells from non-induced animals.

Full Text

Duke Authors

Cited Authors

  • Klaunig, JE; Goldblatt, PJ; Hinton, DE; Lipsky, MM; Trump, BF

Published Date

  • January 1, 1984

Published In

Volume / Issue

  • 12 / 2

Start / End Page

  • 119 - 125

PubMed ID

  • 11478312

Pubmed Central ID

  • 11478312

Electronic International Standard Serial Number (EISSN)

  • 1533-1601

International Standard Serial Number (ISSN)

  • 0192-6233

Digital Object Identifier (DOI)

  • 10.1177/019262338401200202

Language

  • eng