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The Carcinogenicity of Multiple Intragastric Doses of Aromatic and Heterocyclic Nitro or Amino Derivatives in Young Female Sprague-Dawley Rats

Southern Research Institute (D. P. G.) and Birmingham Baptist Hospital (A. E. C.),¹ Birmingham, Alabama 35205, and National Cancer Institute (E. K. W., J. H. W.), Bethesda, Maryland 20014

The carcinogenicity of 35 compounds was evaluated in young female Sprague-Dawley rats 9 months after the oral feeding of 10 doses at the maximally tolerated level. The following compounds were definitely active in causing breast cancer: 2-anthramine, 2,7-fluorenediamine, benzidine, N-6-(3,4-benzo-coumarinyl)acetamide, [-(2-methylhydrazino)toluoyl]urea, and 7,12-dimethylbenz[]anthracene, the positive control. Weaker responses were elicited by tolidine, thiodianiline, and 1-chloro-2,4-dinitronaphthalene. Biphenyltetramine, 1,3,7-tribromo-2-fluorenamine, 1-anthramine, and nitrofurazone led to a borderline response. One of 132 negative control rats had breast cancer.

Single lesions at sites other than the breast, not present in controls, were observed in rats administered: 4,4'-oxydianiline, 4,4'-sulfonyldianiline, 1,3,7-tribromo-2-fluorenamine, 2-anthramine, 1-anthramine, 1-methylaminoanthraquinone, N-methyl-N-2,4,6-tetranitroaniline, N-6-(3,4-benzocoumarinyl)acetamide, diphenylthiohydantoin,[-(2-methylhydrazino)toluoyl]urea and 7,12-dimethylbenz[]anthracene.

2-Aminoanthraquinone induced cystic changes in the kidneys in a high percentage of the treated rats.

Mammary cancer induction in young female Sprague-Dawley rats is a rapid and sensitive technic for detection of the carcinogenicity of polynuclear aromatic hydrocarbons, of polycyclic nitro and amino derivatives, and also of select heterocyclic compounds. Multiple dosing was no more sensitive than a single large dose for pinpointing active compounds. However, repeated treatments increased the percentage of tumor-bearing animals and the multiplicity of the tumors with active compounds.

¹ Research performed under Contract No. PH43-64-66 from the National Institutes of Health.

Received 10/23/67. Accepted 1/13/68.