Alterations in 3H-thymidine incorporation into DNA induced by methyl CCNU (1-(2-chloroethyl)-3-(4-methyl cyclohexyl)-1-nitrosourea) in normal and tumorous tissues in vivo.
Methyl CCNU produces a suppression of tritiated thymidine (3H-TdR) incorporation into DNA in vivo in normal bone marrow and gastrointestinal tissues which is different in magnitude and duration from that seen in L1210 ascites tumor in the same animals. This suppression and recovery pattern is not seen in animals bearing L1210 ascites tumor resistant to MeCCNU. Where a different pattern of recovery is seen between normal host target tissues and tumor, the pattern can be exploited to increase the cure rate of animals bearing advanced L1210 ascites tumor with properly spaced second doses of MeCCNU. Additional information on the potential toxicity of second doses of MeCCNU can be predicted from knowledge of the time of recovery of DNA synthesis in the normal host target tissues.
D000818:Animals; D001853:Bone Marrow / Q000378:metabolism*; D004247:DNA / Q000096:biosynthesis*; D004273:DNA, Neoplasm / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D007413:Intestinal Mucosa / Q000378:metabolism*; D007700:Kinetics; D007939:Leukemia L1210 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009607:Nitrosourea Compounds / Q000494:pharmacology*; D012673:Semustine / Q000494:pharmacology* / Q000633:toxicity; D013936:Thymidine / Q000378:metabolism
D004273:DNA, Neoplasm; D009607:Nitrosourea Compounds; D012673:Semustine; D004247:DNA; D013936:Thymidine