lahedwith lethal toxicity, myelotoxicihy, and L1210 leukemia anhilumon activity in mice. The role of waler solubility in determining L1210 leukemia antitumon activity and munine

Linear regression analysis was performed ho study the correlation of in vitro carbamoylating activities, alkylating activities, and chemical half-lives with the biological activi lies of six chloroethylnitrosouneas in mice. The biological parameters included the dose resulting in the death of 10% of normal mice (LD,1), anhitumon activity for the L1210 leu kemia system , and myelotoxicity as expressed by the nadir of the peripheral blood neutnophil count following an LD,) dose. There was a highly significant inverse linear relationship between alkylahing activity and the chemical half-life of the chlonoelhylnihrosoureas. A significant linear relationship was found between the molar LD,1@and alkylating activity on the chemical half-life; the greater the alkylating activity on the shorter the half-life, the lower the molar LD,@,. In con trash, carbamoylating activity did not demonstrate a signifi cant correlation with the molar LD111. None of the three chemical parameters demonstrated a significant linear correlation with anlihumor activity on mye lotoxicity. Water solubility did not function as an independ ent variable for either of these biological activities. Two agents in this series, chlorozotocin and 1-(2-chloroethyl)-3(/3-D-glucopyranosyl)-1 -nilnosounea, produced no suppres sion of the peripheral blood neulnophil count at an LD11 dose; both have a glucose carrier that may be responsible for their reduced myeloloxicity.