Osamu Hirai

Antitumour Activity of Purified Arabinogalactan-peptidoglycan Complex of the Cell Wall Skeleton of Rhodococcus lentifragmentus

Antitumour activity of arabinogalactan peptidoglycan (AP) complex (peptidoglycan and arabinogalactan liberated by an acid or alkaline treatment from Rhodococcus lentifragmentus AN-115 cell wall skeleton) was examined in mice and compared with that of the cell wall skeleton. The growth of syngeneic fibrosarcoma Meth A cells after implantation in BALB/c mice was significantly suppressed by AP complex, and also regressed after intratumoral injection of AP complex on days 1, 4 and 7 after tumour implantation. Although the activity of peptidoglycan was less than that of AP complex, peptidoglycan also showed both tumour-suppressive and regressive activities. Arabinogalactan did not show antitumour activity. It is interesting that peptidoglycan has an important role in the effect against tumours.

Microbial mutagenicity and in vitro chromosome aberration induction by FK973, a new antitumor agent

The genotoxic activity of a new antitumor agent, FK973, was compared with that of mitomycin C (MMC) in eukaryotic and prokaryotic cells. In chromosome aberration tests using Chinese hamster fibroblast Don cells, FK973 induced a dose-related increase of aberrant cells after 6 h-pulse treatments, and the minimum effective concentrations with and without S9 were 0.625 and 0.0625 micrograms/ml, respectively. The compound increased revertant colonies in Salmonella typhimurium TA102 at the dose range of 10-5000 micrograms/plate with S9. Without S9, FK973 induced a small increase at the dose range of 500-5000 micrograms/plate in two of three independent experiments, but the number of revertant colonies was less than double that of the vehicle control. The compound did not induce any revertant colonies in colonies in S. typhimurium TA100, TA98, TA1535 or TA1537 with or without S9. MMC was confirmed to increase both chromosome aberrations in Don cells and revertant colonies in TA102. The minimum clastogenic and mutagenic concentrations without S9 were 0.0156 microgram/ml and 0.005 microgram/plate, respectively. The results indicate that FK973 needs metabolic activation to induce reverse mutation in prokaryotic cells, but caused chromosome aberrations in mammalian cells without added S9.

[Host mediated anti-tumor effect of Nocardia rubra cell wall skeleton on syngeneic tumor in mice].

The mode of action of Nocardia rubra cell wall skeleton (N-CWS) on Meth A fibrosarcoma (Meth A) was studied in BALB/c mice. N-CWS suppressed or regressed the intradermal growth of syngeneic Meth A cells in normal BALB/c and athymic BALB/c mice. The intradermally and subcutaneously infiltrated cells harvested from injection sites of N-CWS in normal mice showed in vitro cytotoxic activity against Meth A cells. Pretreatment of normal BALB/c mice with immunosuppressing agents such as hydrocortisone, carrageenan, or silica particles significantly reduced the anti-tumor effect of N-CWS. The growth of Meth A cells, rechallenged into BALB/c mice in which Meth A cells had once been suppressed or regressed by N-CWS treatment, was also inhibited, but not in similarly treated athymic nude mice. This resistant mechanism was shown to be dependent out cellular components but not on humoral components by the Winn Assay. The present results suggest that N-CWS exerts its anti-tumor activity by mediation of the immune system of the host and that the main effector cells in the early stage of tumor rejection are macrophages; T cells may also be involved in the later stage.