Modes of genotoxicity of a macromolecular antibiotic, SN-07, a novel type of interstrand DNA cross-linker.

The modes of genotoxicity of a novel macromolecular antitumor antibiotic (SN-07) were examined using both prokaryotic and eukaryotic cells in vitro. The antibiotic induced a frameshift-type reverse mutation in Ames Salmonella typhimurium TA98 at 1.6-400 ng/plate with and without S9 mix.

Mechanisms of action of a novel macromolecular antitumor antibiotic, SN-07, on mouse leukemia L1210 cells in culture.

The mechanisms of action of a novel macromolecular antitumor antibiotic (SN-07) were examined using cultured mouse lymphoid leukemia L1210 cells. A shoulder exponential-type cytotoxicity was observed when the cells were treated with 3.13 to 100 ng/ml SN-07 for 1 hr and surviving colonies were counted after a 14-day incubation.

A novel macromolecular antibiotic, SN-07. Taxonomy of producing organism, isolation, characterization and biological activities.

A novel macromolecular antibiotic SN-07 was obtained from the cultural supernatant of Actinomadura roseoviolacea var. miuraensis nov. var.

Antitumor activities of harringtonine and homoharringtonine, cephalotaxus alkaloids which are active principles from plant by intraperitoneal and oral administration.

Antitumor activities of harringtonine(HA) and homoharringtonine(HO) both belong to cephalotaxus alkaloids were compared with those of vinca alkaloids, vincristine (VCR) and vinblastine (VLB). HA and HO had significant activities against P388 leukemia, L1210 leukemia and B16 melanoma by intraperitoneal injection comparable to VCR and VLB. The therapeutic index (LD10/ED50) of HA and HO in B16 melanoma system was 1.

Reverse mutation tests in Salmonella typhimurium and chromosomal aberration tests in mammalian cells in culture on fluorinated pyrimidine derivatives.

Reverse mutation (Ames) tests with Salmonella typhimurium TA98, TA100 and TA1537, and chromosomal aberration tests in vitro with a Chinese hamster fibroblast cell line (CHL), were carried out on fluorinated pyrimidine derivatives, such as 5-fluorouracil (5-FU), 1-(2-tetrahydrofuryl)-5-fluorouracil (FT), 5-fluorodeoxyuridine (FUdR), 1,3-bis(2-tetrahydrofuryl)-5-fluorouracil (FD-1) and a mixture of uracil and FT in the molar ratio 4 : 1 (UFT) (Fujii et al., 1978). For comparison, similar tests were also carried out on 4 anti-metabolic agents, a metabolite of FD-1 and a component of UFT, such as cytosine-1-beta-D-arabinofuranoside (AraC), 6-mercaptopurine (6-MP), 6-thioguanine (6-TG), 8-azaguanine (8-AG), 3-(2-tetrahydrofuryl)-5-fluorouracil (3-FT) and uracil.