Modification by WR 2721 of the response to chemotherapy of tumours and normal tissues in the mouse.

P R Twentyman

doi:10.1038/bjc.1983.7

Abstract

The sulphydryl compound WR 2721 has been combined with a range of cytotoxic drugs in the mouse and the effects upon tumours and normal tissues determined. In the acute lethality (LD50/30) assay, mean protection factors produced by WR 2721 (200 or 400 mg kg-1) were generally less than 1.3 for cyclophosphamide (CTX), CCNU and chlorambucil (CHL) but a protection factor of 1.7 was obtained for cisplatinum (cis-P) in combination with 400 mg kg-1 of WR 2721. No protection against the depression of peripheral white cell count seen at 3 days after CTX, CCNU or cis-P was obtained with either 200 or 400 mg kg-1 of WR 2721. Significant protection of the RIF-1 sarcoma by WR 2721 against CTX and cis-P induced growth delay was seen. In the KHT sarcoma, WR 2721 produced small reductions in the growth delay caused by CCNU, melphalan and CHL but these were not statistically significant. These data show less differential normal tissue protection by WR 2721 than do a number of reports in the literature.

Highlights

In our own study of cyclophosphamide (CTX) in combination with WR 2721, we found significant protection of two mouse tumours against CTX, whilst seeing less protection of normal tissues than reported by others (Twentyman, 1981)
Tumours used were the KHT and RIF-1 sarcomas, both of which originated in C3H/Km mice at Stanford University, California, and which have been previously described (Kallman et al, 1967; Twentyman, et al, 1980)
These data are based on results of experiments in which 6 groups of 5 mice were treated with graded doses of the cytotoxic drugs

Summary

Mice and tumours

The mice used in these studies were inbred C3H/He supplied by OLAC. Females were used in most experiments, but males were used occasionally. Tumours used were the KHT and RIF-1 sarcomas, both of which originated in C3H/Km mice at Stanford University, California, and which have been previously described (Kallman et al, 1967; Twentyman, et al, 1980). Most of the experiments were carried out with a sample of batch NF LOT AJ 68.2 supplied in December 1979. We have recently (March 1982), obtained a sample of batch NH LOT AJ 68.4 and this was used in a number of experiments specified in the Results section. Both specimens arrived packed with dry ice and were subsequently kept at -20°C.

Results

Chester Beatty Research Institute

White cell count

Tumour response