Disease relevance of CHLOROZOTOCIN

• Administration of polyinosinic-polycytidylic acid with CZT restored the NK cell cytotoxicity of LIC and inhibited lung metastases amplification [1].
• Administration of repeated high doses of 7.5 mg chlorozotocin [(CZT) CAS: 54749-90-5]/kg to syngeneic WAG rats bearing the rhabdomyosarcoma 9-4/0 enhanced the incidence of spontaneous metastasis compared to its incidence in untreated rats [1].
• It was observed that a single injection of 20 mg/kg body weight of BCNU or CLZ, even at an advanced stage of tumor growth, completely cured greater than 90% of the tumor-bearing mice [2].
• Following treatment of tumor-bearing mice with BCNU or CLZ, tumor-specific delayed type hypersensitivity responses were demonstrable in these mice but not in STZ-treated mice [2].
• Both derived lines proved to be more aggressive than the parental, proliferated more rapidly, and were resistant to CZT toxicity [3].

High impact information on CHLOROZOTOCIN

• However, when alkylations are measured per microgram of protein, the ratio of covalently bound drug to RNP:matricin was 1.2 for both CLZ and CCNU [4].
• Alkylation of the nuclear matrix by chlorozotocin (CLZ) or 1-(2-chloroethyl-3-cyclohexyl)-1-nitrosourea (CCNU) was 1.58 and 1.27 pmoles drug/micrograms protein, respectively, whereas carbamoylation by CCNU was 32.5 pmoles/micrograms [4].
• Also, addition of growth factors such as IL-1, IL-2, IL-4 and IL-6 failed to reconstitute the defective responsiveness of BCNU- and CLZ-treated T cells and macrophages [5].
• Treatment of C57BL/6 mice with 5 intraperitoneal injections of 20 mg/kg body weight of BCNU or CLZ caused an increase in the percentage of CD4(-)CD8- T cells and a decrease in the percentage of CD4(+)CD8+ T cells in the thymus [5].
• When T cells in the spleens of nitrosourea-treated mice were functionally analysed, it was observed that BCNU and CLZ caused a dramatic decrease in the T cell responsiveness to ConA, anti-CD3 and phorbol myristate acetate plus calcium ionophore stimulation [5].

Chemical compound and disease context of CHLOROZOTOCIN

• Although SZ-induced toxicity was ameliorated with addition of nicotinamide to cultures of beta cells, nicotinamide did not prevent damage caused by CLZ [6].

Biological context of CHLOROZOTOCIN

• There were considerable differences in tumor-inhibitory activity, with HeCNU ranking first and CZT last, and the rank order was similar for drug-induced lethality or bone marrow damage (in terms of reduced cellularity or macromolecular DNA damage) [7].
• Two CZT-resistant lines, R3 and R9, showed no common aberration, but R9 which was most resistant, was shown to have a homogeneously staining region, which is usually thought to be the site of gene amplification [8].

Anatomical context of CHLOROZOTOCIN

• Using the accessory cell-dependent and -independent assays, BCNU and CLZ were found to suppress the functions of both T cells and macrophages [5].

References