Premature Chromosome Condensation Frequencies in Human Peripheral Blood Lymphocytes in vitro Treated with Melphalan

Jenõ Major, Mátyás G. Jakab and Anna Tompa

József Fodor National Center for Public Health, National Institute of Chemical Safety, Budapest, Hungary
 
Corresponding author: Dr. Jenõ Major
József Fodor National Center for Public Health
National Institute of Chemical Safety
H-1450 Budapest
P. O. Box 36, Hungary
Tel: (+36) 1 215-7890,
Fax: (+36) 1 215-2904
E-mail: j_major@mailexcite.com

 
CEJOEM 1999 5(2):142-147
ABSTRACT
: In vitro melphalan treatment induced premature chromosome condensation (PCC, i. e., a co-existence of a mitotic phase nucleus with another nucleus at a different stage of the cell cycle) frequencies were investigated in peripheral human lymphocytes (PBLs) of a male donor in order to study the feasibility of PCC as a possible end-point in the human genotoxicology monitoring as PCC probably has importance in the etiology of human malignant diseases. PBLs were treated with 0, 10–7, 10–6 and 10–5 M melphalan and structural chromosome aberration (CA) and PCC frequencies were parallel scored in 200 metaphases in each melphalan concentration. In the present study, melphalan treatment failed to induce PCC although it was a potent CA inducer in the same cells. PCC is considered a manifestation of cell fusion, when the non-metaphase chromatin condenses into chromosomes and the nuclear membrane dissolves. Similarly to viruses, chemical and physical agents also can induce PCC both in vivo and in vitro and PCC was observed in different human populations occupationally exposed to various genotoxic chemicals, predominantly alkylating agents. The present results suggest that non-clastogenic mutagenic chemicals such as alkylating agents are probably less successful PCC inducers than clastogens. The obtained low PCC yields, both after in vivo exposure or in vivo treatment, to alkylating chemicals also suggest that PCC inducibility (without cell fusion inducers) is not a suitable end-point for the purposes of human genotoxicology monitoring.

KEY WORDS: Alkylating agents, chromosome aberrations, genotoxicology monitoring, risk assessment


Acknowledgement
The authors thank Mrs. Andrea Herczeg-Tóth and Mrs. Irén Rétháti for the excellent assistance. This work was financially supported by the grant of Ministry of Health and Social Welfare, Hungary, ETT T-08 241/96.
Received: 03 May 1999
Accepted: 09 June 1999

Posted: December 1999

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