Comparative study on Salmonella mutagenicity and on cytogenetic and antineoplastic effects induced by cyclophosphamide and 3-aminobenzamide in cells of three transplantable tumours in vivo.

Synergistically enhanced sister chromatid exchange (SCE) frequency by cyclophosphamide (CP) was observed when L1210 lymphoid tumor cells were exposed in vivo to a non-toxic concentration of 3-aminobenzamide (3-AB). Additive effects in SCE induction in vivo were observed when either Ehrlich ascites tumor (EAT) cells or P388 lymphocytic leukemia cells treated with CP were exposed to 3-AB in vivo. 3-AB enhanced the survival time of L1210 tumor bearing BDF1 mice treated with CP. However, the combined CP plus 3-AB treatment did not increase the survival of either EAT BALB/c- or P388 BDF1-tumor bearing mice compared with the effect on survival by CP alone. Therefore the in vivo differential antitumor effect, by CP in conjunction with 3-AB, appears to correlate well with the in vivo differential effect on cytogenetic damage caused by the combined CP plus 3-AB treatment. In the Salmonella typhimurium/mammalian microsome test CP appears to have a dose dependent ability to induce base-pair substitutions in strains TA 100 and TA 1535 and frameshift mutations in strains TA 98 and TA 1537. Both types of mutation were synergistically increased in the presence of 3-AB.