Reference

Enhancement of induced sister chromatid exchange and chromosomal aberrations by inhibitors of DNA repair processes

Enhancement of induced sister chromatid exchange and chromosomal aberrations by inhibitors of DNA repair processes. Palitti, Fabrizio; Tanzarella, Caterina; Degrassi, Francesca; De Salvia, Rosella; Fiore, Mario (Cent. Genet. Evoluzion., Cons. Naz. Ric., Rome, Italy). Toxicol. Pathol., 12(3), 269-73 (English) 1984. CODEN: TOPADD. ISSN: 0192-6233. DOCUMENT TYPE: Journal CA Section: 4 (Toxicology) The effect of posttreatment with inhibitors of DNA synthesis (hydroxyurea [127-07-1], aphidicolin [38966-21-1]) and repair (caffeine [58-08-2], 3-aminobenzamide [3544-24-9]) on the frequencies of chromosomal aberrations and sister chromatid exchange (SCE) induced by mitomycin C (I) [50-07-7] and decarbamoylmitomycin C [26909-37-5] was studied in vitro in Chinese hamster cells and in human lymphocytes. The data show that in the case of Chinese hamster and human lymphocyte I-treated cells there was an increased frequency of both chromosomal aberrations and SCE after a G2 posttreatment with the inhibitors, whereas no increase was obsd. for decarbamoyl mitomycin C-treated cells. Since SCE is a DNA synthesis-dependent phenomenon, an increase in the frequency of SCE also in the G2 phase might suggest that after I treatment there is a residual DNA synthesis still going on very late in the cell cycle.

Cyclophosphamide resistance developed in a human melanoma cell line

Cyclophosphamide resistance developed in a human melanoma cell line. Boon, Mark H.; Parsons, Peter G. (Queensland Inst. Med. Res., Herston, Australia). Cancer Treat. Rep., 68(10), 1239-40 (English) 1984. CODEN: CTRRDO. ISSN: 0361-5960. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Section cross-reference(s): 8 The Mer- human melanoma cell line MM253c1 was treated 4 times with cyclophosphamide [50-18-0] activated in situ with rat liver microsomes, the fourth cycle being preceded by treatment with the mutagenic methylating agent N-methyl-N1-nitro-N-nitrosoguanidine [70-25-7]. The resulting subline (MM253c1-4CG) showed increased resistance to activated cyclophosphamide; the resistance of 7 allogeneic human tumor lines and of a fibroblast strain spanned the 2 extremes represented by the autologous MM253c1 lines. MM253c1-4CG cells were highly resistant to killing by methylating agents, a property indicative of conversion of the Mer+ phenotype. Compared with the parent line, MM253c1-4CG cells were resistant to DNA cross-linking agents having different structures and transport mechanisms (melphalan [148-82-3], mechlorethamine [51-75-2], and mitomycin [1404-00-8]) and were slightly more resistant to doxorubicin [23214-92-8], gamma rays, and hydroxyurea [127-07-1] but were not resistant to killing by acrolein [107-02-8], cytarabine [147-94-4], H2O2, 254 nm UV, [3H]thymidine [2792-47-4], vincristine [57-22-7]. No difference in the intracellular concn. of potential alkylation targets (RNA, protein, and SH groups) was found, and neither cell line appeared able to activate cyclophosphamide or detoxify its metabolites. Caffeine [58-08-2] and 3-aminobenzamide [3544-24-9] had no synergistic effect upon cyclophosphamide toxicity in either cell line. 3-Aminobenzamide showed synergism with the methylating agent 5-(3-methyl-1-triazeno)imidazole-4-carboxamide [3413-72-7], the effect being greater in MM253c1-4CG than in MM253c1 cells. These results suggest that in vitro activation of cyclophosphamide produces a metabolite similar in stability to phosphoramide mustard [10159-53-2], resistance to such toxicity being assocd. not with conversion to the Mer+ phenotype but with some intracellular change which confers resistance to a variety of DNA cross-linking agents.