Growth and rejection patterns of murine lymphoma cells antigenically altered following drug treatment in vivo

Abstract

Murine leukemia cells transformed by in vivo treatment with 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC) are rejected by histocompatible recipients following inocula of 10(7) cells i.p. Progressive tumor growth or tumor growth and regression was monitored measuring the extent of DNA synthesis in the peritoneal cavity of mice using the [125I]5-iodo-2'-deoxyuridine uptake method. In addition, the results were confirmed by cell count and mortality data. Comparable growth rate was found initially in both DTIC and parental lines in histocompatible hosts. Later, mice challenged with parental lines died, whereas hosts inoculated with DTIC-treated sublines rejected the tumor. On the other hand, lethal growth occurred in mice inoculated with DTIC-treated sublines when immunodepressed by cyclophosphamide given before tumor challenge, or by methotrexate given after challenge of a methotrexate-resistant DTIC-treated subline. The similarity between the growth rate of the parental and DTIC-treated lines in histocompatible hosts does not support the hypothesis of impaired "oncogenic potential" of such DTIC-treated lines. Furthermore, the growth and rejection pattern of a parental line in H-2-incompatible hosts was similar to that observed for DTIC-treated lines in histocompatible hosts, suggesting that comparable immune mechanisms were involved in both cases.