Can lowLET Radiation from Incorporated Radionuclides Induce Mutagenic Effects in Unirradiated Bystan

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Can low-LET Radiation from Incorporated
Radionuclides Induce Mutagenic Effects in
Unirradiated Bystander Cells?Marek Lenarczyk,
Helene Z. Hill, and Roger. W. Howell.  Department
of Radiology, New Jersey Medical School, Newark,
NJ 07103
ABSTRACT Recent evidence suggests that cells
irradiated with high-LET particles can impart
mutagenic effects to unirradiated bystander
cells. However, these bystander mutagenic
effects have not yet been reported for low-LET
radiation emitted by incorporated radionuclides.
The present study investigates whether mutagenic
effects, namely induction of HPRT- mutations in
V79 cells, can be induced in bystander cells that
are adjacent to cells containing tritiated
thymidine (3HdThd). Chinese hamster V79 lung
fibroblasts are labeled with 3HdThd, mixed with
and equal number of unlabeled cells, and a
multicellular cluster (1.6 mm in diameter) is
formed by gentle centrifugation of the mixed
cells. The short-range of the ?-particles emitted
by 3H imparts only self-irradiation of labeled
cells without any cross-irradiation of unlabeled
(bystander) cells. The clusters are maintained
at 10.5?C for 72 h, dismantled, and 2x106 cells
are plated for mutant expression. After 15 days,
2x105 cells are seeded into P100 dishes and
incubated for 12-14 days for HPRT- mutant
selection in the presence of 6-thioguanine. The
mutant frequency is is equal to 1.3x10-6 mutant
bystanders per Gy in the labeled cells. These
studies provide new data on the mutagenic effects
of nonuniform distributions of radioactivity that
may have implications for both diagnostic and
therapeutic applications of radionuclides.
CONCLUSIONS The present studies use a novel three
dimensional cell culture system to show that
cells that are chronically irradiated by low
energy electrons from incorporated radioactivity
can impart mutagenic effects in neighboring
bystander cells that neither contain
radioactivity nor are significantly irradiated by
their radioactive neighbors. This is important
because whenever radioactivity is incorporated
into tissues in vivo, it invariably is
distributed nonuniformly at both the macroscopic
and multicellular levels. Therefore, these data
suggest that individual cells within a population
containing a nonuniform distribution of
radioactivity may incur a risk not only from the
radiation exposure that they may receive, but
also from bystander effects imparted by
neighboring cells.