This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Vesselinovitch, S. D. Articles by Mihailovich, N. Search for Related Content PubMed PubMed Citation Articles by Vesselinovitch, S. D. Articles by Mihailovich, N.

Factors Modulating Benzidine Carcinogenicity Bioassay¹

Departments of Radiology [S. D. V., K. V. N. R., N. M.] and Pathology [S. D. V.], The Pritzker School of Medicine, and Franklin C. McLean Memorial Research Institute [S. D. V.], The University of Chicago, Chicago, Illinois 60637

An integrated series of studies was presented in which several factors were assessed as to their capability to influence the outcome of carcinogenicity of benzidine dihydrochloride in mice. In all studies C57BL/6J x C3HeB/FeJ F₁ mice of both sexes were utilized. Animals were either 6 or 1 week of age at the beginning of carcinogenic treatment. Six-week-old mice were exposed to p.o. administration of carcinogen delivered either in food (50 or 100 ppm daily) or by stomach intubation at equivalent dose levels at twice-weekly intervals. In addition, a 150-ppm dose level in food was administered for 39, 54, or 84 weeks. A limited 3-week, daily intubation of benzidine (30 or 100 µg/mouse) was also explored in 1- and 6-week-old mice. Animals were killed in all studies at 90 weeks of age, at which time their tumor incidence was evaluated.

Depending upon experimental conditions, benzidine treatment effected development of liver tumors, lung adenomas, Harderian gland cystadenomas, and lymphoreticular neoplasms. Continuous feeding of adult mice for 84 weeks at three dose levels of benzidine resulted in development of liver tumors with a positive dose-response relationship in both sexes. The analysis of data revealed a greater susceptibility of females than of males (94% versus 44% at 150 ppm). Twice-weekly administration of benzidine by stomach intubation was shown to be less hepatocarcinogenic than continuous feeding of equivalent amounts. In the series in which male mice were fed food containing 150 ppm of benzidine for only 34 or 54 weeks, in contrast to the above 84-week schedule, a negative relationship was observed between the incidence of liver tumors and the duration of treatment.

Daily administration of 30 µg of benzidine to infants by stomach intubation for a 3-week period significantly enhanced development of liver tumors only in males (66%). Introduction of 150 ppm of benzidine into food offered to mother and offspring from delivery to weaning led to development of liver tumors in 95% of male mice and in 5% of females. No liver tumors developed following similar 3-week treatment of 6-week-old adults.

¹ The investigations have been supported in part by Contracts NIH NCI-E-69-2087 and NO1-CP-43317 and by Carcinogenesis Research Grant from the Upjohn Company. Presented at the Third Annual Carcinogenesis Collaborative Conference, National Cancer Institute, Division of Cancer Cause and Prevention, February 2 to 5, 1975, Orlando, Fla.

Received 3/ 3/75. Accepted 7/ 8/75.