Mutagenic and chemotherapeutic activity in L1210 leukemia of several monofunctional alkylating agents Journal Article
| Authors: | Schmid, F. A.; Otter, G. M.; Mehta, B. M. |
| Article Title: | Mutagenic and chemotherapeutic activity in L1210 leukemia of several monofunctional alkylating agents |
| Abstract: | The mutagenic and chemotherapeutic activities of the following monofunctional alkylating agents were compared in vivo: β -chloroethylamine, dimethyl- and diethylaminoethyl chloride; methyl- and ethylmethanesulfonate; methyl- and ethylnitroso-urea; and procarbazine. The bifunctional alkylating agent diethyl-amine 2,2'-dichloro-/V-methyl-hydrochloride was used as reference. The alkylating activity was assessed by reacting with 4-(p-nitrobenzyl)pyridine, and antitumor activity was determined against L1210 in vitro and in vivo. The L1210 response, which is consistent with useful alkylating reactivity, was very marked with the two nitrosoureas and procarbazine. The nitrosoureas and, to some extent, procarbazine decreased the tumorigenicity of L1210 leukemia as evidenced by the increase in survival times with increasing numbers of treatment generations. After treatment for about five transfers (106 cells i.p.) with methylnitroso-urea (40 mg/kg i.p. on Days 1, 3, and 5), the untreated control mice consistently survived free of tumor, whereas the treated mice died before Day 30. After treatment with ethylnitrosourea (80 mg/kg), the survival times also increased but more in the treated than in the corresponding control groups. Methylnitro-sourea was most efficient in increasing the survival times and abolishing tumor transplantability. Antigenic change and loss of growth potential presumably were the reason for this increase in survival time, as indicated by tests in X-irradiated and nude mice. The fact that nitrosoureas and triazenes, besides reducing tumorigenicity, have similarities in their chemistry in that they decompose or are metabolically converted into diazohydroxides and then to carbonium ions is possibly of significance. © 1985, American Association for Cancer Research. All rights reserved. |
| Keywords: | cancer chemotherapy; mutation; cancer combination chemotherapy; nonhuman; antineoplastic agents; comparative study; mouse; animal; mice; heredity; animal model; alkylating agent; in vitro study; drug resistance; structure-activity relationship; chlormethine; procarbazine; mice, inbred strains; mice, nude; alkylating agents; therapy; ethylnitrosourea; mutagenesis; chlormethine derivative; mutagens; nitrosourea derivative; mesylic acid methyl ester; methylnitrosourea; chemical mutagenesis; leukemia l1210; chemical carcinogenesis; priority journal; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; mesylic acid ethyl ester; blood and hemopoietic system; 2 chloroethylamine; diethylaminoethyl chloride; dimethylaminoethyl chloride; sulfonate |
| Journal Title: | Cancer Research |
| Volume: | 45 |
| Issue: | 1 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 1985-01-01 |
| Start Page: | 40 |
| End Page: | 44 |
| Language: | English |
| PUBMED: | 3965147 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 26 October 2021 -- Source: Scopus |
Citation Impact
Related MSK Work