Complete remissions in chemotherapy of lung cancer models induced in mice by asbestos.
Chemotherapy trials were run with mice bearing transplants of carcinomas originally induced from fetal mouse lung cells by asbestos. After treatments with a nitrosourea (PCNU), mice bearing transplants of a large-cell carcinoma (ASB XIV) had complete remissions (CR) in 13 of 20 animals on a 15 mg/kg regimen, in 6 of 20 on an 8 mg/kg regimen, and in none of 10 on a 4 mg/kg regimen. With comparable total doses, treatment was most effective when PCNU was given in a few large doses. In groups where CRs occurred, continued PCNU treatment of animals without CRs prolonged survival but yielded no additional CRs. No CRs of ASB XIV occurred in 80 mice treated with eight other anticancer agents or in 50 controls injected with 0.9% NaCl solution. In mice bearing transplants of a squamous cell carcinoma (ASB XIII), treatments with PCNU were followed by CRs in 3 of 38 animals on 15 mg/kg regimens and in 3 of 28 animals on 8 mg/kg regimens. In groups of 6 mice fed a retinoid (Ro 10-9359) and treated with PCNU, CRs of ASB XIII occurred in 3 animals in each of two trials and in none in a third trial. Ro 10-9359 inhibited growth of transplants of squamous cell carcinoma LC 12 that had been induced from fetal mouse lung cells by a polycyclic hydrocarbon. In trials of four other anticancer agents vs. ASB XIII, CRs occurred only with cyclophosphamide (CPA). There were 7 CRs among 8 mice treated with CPA 100 mg/kg x 3, no CRs in 10 after 100 mg/kg x 2, one CR in 8 after 50 mg/kg x 3, and no CRs in 6 after 50 mg/kg x 4. With the 50 mg/kg x 4 regimen of CPA and 7.5 mg/kg PCNU on the same days, there were 5 CRs in 8 mice. As a single agent, aziridinylbenzoquinone (AZQ) increased life span but gave no CRs. There were CRs of ASB XIII in all of 8 mice after toxic combined therapy with PCNU and AZQ. There were no CRs in 66 control mice bearing ASB XIII.
Smith
William E
WE
Health Research Institute, Fairleigh Dickinson University, Madison, NJ, USA.
Hubert
Doras D
DD
Yazdi
Ebrahim
E
Holiat
Stephen M
SM
Bissell
Elizabeth Cutler
EC
Watts
Laurel Melcher
LM
Baylouny
Raymond A
RA
Sobel
Harold J
HJ
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D017632:Asbestos, Serpentine / Q000633:toxicity*; D001388:Aziridines / Q000008:administration & dosage / Q000627:therapeutic use; D016227:Benzoquinones / Q000008:administration & dosage / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000188:drug therapy* / Q000401:mortality; D002945:Cisplatin / Q000008:administration & dosage / Q000627:therapeutic use; D003961:Dianhydrogalactitol / Q000008:administration & dosage / Q000627:therapeutic use; D008175:Lung Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008942:Mitoxantrone / Q000008:administration & dosage / Q000627:therapeutic use; D023421:Models, Animal; D009607:Nitrosourea Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D015649:Pentostatin / Q000008:administration & dosage / Q000627:therapeutic use; D012074:Remission Induction; D016019:Survival Analysis; D014227:Triazines / Q000008:administration & dosage / Q000627:therapeutic use
D000970:Antineoplastic Agents; D017632:Asbestos, Serpentine; D001388:Aziridines; D016227:Benzoquinones; D009607:Nitrosourea Compounds; D014227:Triazines; D015649:Pentostatin; D003961:Dianhydrogalactitol; C018627:1-(2-chloroethyl)-3-(2,6-dioxo-3-piperidinyl)-1-nitrosourea; D008942:Mitoxantrone; C012071:triazinate; C029108:diaziquone; D002945:Cisplatin