Promotional effects of azathioprine on peripheral B cell lymphomas in BALB/c mice induced by administration of 7,12-dimethylbenz[a]anthracene

BALB/c mice either were injected subcutaneously with 25 μg/g or 50 μg/g body weight 7,12-dimethylbenz[a]anthracene (DMBA) at the age of 13 weeks, or received repeated s.c. injections of azathioprine (0.1 mg/g) starting from the age of 6 or 18 weeks, or they received treatments with both agents. Of the 317 mice treated, 69 developed lymphomas by the age of 50 weeks. None of the 31 non-treated mice developed lymphomas during this period. The lymphomas, classified according to Pattengale-Taylor's classification for murine lymphomas/leukemias, were examined immunohistochemically and immunogenetically. The lymphomas induced with DMBA showed a male preponderance and a higher incidence of the B cell type, especially in the lymph node and spleen. Azathioprine induced predominantly T-lymphoblastic lymphomas in the thymus and these were found more frequently in females. Treatment with both DMBA and azathioprine remarkably increased the incidence of B lymphomas, especially follicular center cell lymphomas in the spleen, which are the predominant type of spontaneous lymphomas occurring in older BALB/c mice. Some of the treated mice also developed prelymphomatous lesions.