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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