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Abstract

COMPARATIVE ANALYSIS OF CYCLOPHOSPHAMIDE MONOHYDRATE CYTOTOXICITY IN HEALTHY HUMAN LYMPHOCYTES AND L5178Y TK+/- MOUSE LYMPHOMA CELLS

Pasula Chandra Sekhar*, Tadakaluru Yasodha Lakshmi, Sannidhi Ranga Suresh, Pujari Venkata Suresh Reddy, Chirumamilla Venkata Satish Kumar, Y. Raja Ratna Reddy

Aptus Biosciences Pvt. Ltd, SVS Medical College, Mahabubnagar, Andhra Pradesh, India.

ABSTRACT

The study was conducted to evaluate and compare the cytotoxicity of cyclophosphamide monohydrate in In vitro Mammalian Chromosome Aberration Test (CAT) using cultured healthy human whole blood lymphocytes and In vitro Cell Gene Mutation Assay (CGM) using L5178Y TK+/- mouse lymphoma cells as per OECD guidelines No. 473 & 476 respectively [1,2], both in the presence (2%v/v) and absence of metabolic activation system. Cyclophosphamide monohydrate is cytotoxic at the doses 250, 125, 62.5, 31.25 μg/ml and non-cytotoxic at 15.62 μg/ml in CGM, where 250, 125, 62.5 μg/ml of doses are cytotoxic and 31.25, 15.62 μg/ml doses are non-cytotoxic in CAT, in the presence of metabolic activation system. Cytotoxicity was not observed in all the test doses 250, 125, 62.5, 31.25, 15.62 μg/ml, in the absence of metabolic activation system both in CGM and CAT. Cyclophosphamide monohydrates require metabolic activation for its cytotoxicity. A lower dose of cyclophosphamide monohydrate is cytotoxic in In vitro Cell Gene Mutation Assay (CGM) than Mammalian Chromosome Aberration Test (CAT) In vitro. Cyclophosphamide monohydrate is non cytotoxic in both assays, in the absence of metabolic activation system indicates that metabolic activation system play a key role in the cytotoxicity of cyclophosphamide monohydrate.

Keywords: Cyclophosphamide monohydrate, Cytotoxicity, metabolic activation.


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