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Carcinogen induced unscheduled DNA synthesis in mouse hepatocytes.

Publication ,  Journal Article
Klaunig, JE; Goldblatt, PJ; Hinton, DE; Lipsky, MM; Trump, BF
Published in: Toxicologic pathology
January 1984

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.

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Published In

Toxicologic pathology

DOI

EISSN

1533-1601

ISSN

0192-6233

Publication Date

January 1984

Volume

12

Issue

2

Start / End Page

119 / 125

Related Subject Headings

  • Toxicology
  • Time Factors
  • Thymidine
  • Phenobarbital
  • Mice, Inbred BALB C
  • Mice
  • Male
  • Hepatocytes
  • Enzyme Induction
  • Dose-Response Relationship, Drug
 

Citation

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Klaunig, J. E., Goldblatt, P. J., Hinton, D. E., Lipsky, M. M., & Trump, B. F. (1984). Carcinogen induced unscheduled DNA synthesis in mouse hepatocytes. Toxicologic Pathology, 12(2), 119–125. https://doi.org/10.1177/019262338401200202
Klaunig, J. E., P. J. Goldblatt, D. E. Hinton, M. M. Lipsky, and B. F. Trump. “Carcinogen induced unscheduled DNA synthesis in mouse hepatocytes.Toxicologic Pathology 12, no. 2 (January 1984): 119–25. https://doi.org/10.1177/019262338401200202.
Klaunig JE, Goldblatt PJ, Hinton DE, Lipsky MM, Trump BF. Carcinogen induced unscheduled DNA synthesis in mouse hepatocytes. Toxicologic pathology. 1984 Jan;12(2):119–25.
Klaunig, J. E., et al. “Carcinogen induced unscheduled DNA synthesis in mouse hepatocytes.Toxicologic Pathology, vol. 12, no. 2, Jan. 1984, pp. 119–25. Epmc, doi:10.1177/019262338401200202.
Klaunig JE, Goldblatt PJ, Hinton DE, Lipsky MM, Trump BF. Carcinogen induced unscheduled DNA synthesis in mouse hepatocytes. Toxicologic pathology. 1984 Jan;12(2):119–125.
Journal cover image

Published In

Toxicologic pathology

DOI

EISSN

1533-1601

ISSN

0192-6233

Publication Date

January 1984

Volume

12

Issue

2

Start / End Page

119 / 125

Related Subject Headings

  • Toxicology
  • Time Factors
  • Thymidine
  • Phenobarbital
  • Mice, Inbred BALB C
  • Mice
  • Male
  • Hepatocytes
  • Enzyme Induction
  • Dose-Response Relationship, Drug