Changes of host cell infiltration into Meth A fibrosarcoma tumor during the course of regression induced by injections of a BCG nucleic acid fraction.
MY-1, which consists of DNA and RNA extracted and purified from Mycobacterium bovis strain BCG, causes the regression of various experimental syngeneic tumors when injected intratumorally. In order to identify the host cells involved in the antitumor mechanism(s) of MY-1, we examined Meth A tumors inoculated intradermally to BALB/c mice, which were given multiple injections of MY-1 following tumor inoculation. Histological and immunohistochemical examinations were performed at several time points. On day 4 after inoculation, the MY-1-treated tumors were heavily infiltrated with a heterogeneous population of mononuclear cells with low density nuclei. The MY-1-injected tumors contained asialo-GM1-positive cells and Mac-1-positive cells, which indicated that the infiltrating mononuclear cells were natural killer cells and macrophages. On day 14 after inoculation, the tumors were infiltrated with a large number of L3T4-positive cells and fewer Lyt-2-positive cells, both of which were more abundant in the MY-1-treated tumors than in the control tumors. The observed sequence of host cell infiltration corresponded well with our previous studies which have indicated that the antitumor mechanism of MY-1 is divided into two phases, i.e. the early phase when natural killer cells and macrophages inhibit tumor growth, and the late phase when L3T4-positive cells act to induce tumor regression via a delayed-type hypersensitivity against tumor cells.
Kuramoto
E
E
Institute of Biological Science, Mitsui Pharmaceuticals, Inc., Chiba, Japan.
Watanabe
N
N
Iwata
D
D
Yano
O
O
Shimada
S
S
Tokunaga
T
T
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D004269:DNA, Bacterial / Q000494:pharmacology*; D005260:Female; D005354:Fibrosarcoma / Q000473:pathology*; D007155:Immunologic Factors / Q000494:pharmacology*; D008748:Methylcholanthrene; D051379:Mice; D008807:Mice, Inbred BALB C; D009163:Mycobacterium bovis / Q000737:chemistry*; D009368:Neoplasm Transplantation; D012329:RNA, Bacterial / Q000494:pharmacology*
D000945:Antigens, Differentiation, T-Lymphocyte; D004269:DNA, Bacterial; D007155:Immunologic Factors; D012329:RNA, Bacterial; D008748:Methylcholanthrene