Environmental and Molecular Mutagenesis - Legacy Tobacco ...

128 1989 EMS Abstracts
Notes
http://legacy.library.ucsf.edu/tid/clb93d00/pdf
367
DHYDRO7CY-2(5H)~F~gT~Ip ONE (MX ~FJ I~R ~Na ier`, A .ID . CDsAna 1o13-FH B .RDaniel1C K~~Schenck1,
M . F . Ske~ly2 and S . L . HuangZ lU .S . Environmental Protection Agency, Cincinnati,
OH 45268, Environmental Health Research and Testing, Cincinnati, OH 45245 NC 27709 .
MX is a potent bacterial mutagen and mammalian cell clastogen that forms in drinking
water during water chlorination . Concern over potential health hazards stems from the
finding that !DC is a major contributor to the mutagenic activity of drinking water samples .
The present work was done to obtain preliminary information on the nature of the DNA
damage which accounts for the potent genotoxic activity of MX . DNA adduct formation
was examined in Salmonella tyohimurium TA100 cells, primary rat hepatocytes, nd in a
rat liver embryonic cell line (Clone 9) . DNA adducts were anal~zed by the 3~P-postlabeling
method of Randerath and Gupta . Mutation frequency (his revertants) was also
determined for the TA100 cells . The Salmonella cells were exposed to !D( concentrations
of 0, 1 and 3 pg/ml for 30 min . at 37°C whereas the mammalian cells were exposed for 6
hr to concentrations of 0, 1, 5, 10 and 50 pg/ml . Mutation induction was linear over
this dose range in the Salmonelia cells, whereas higher concentrations were toxic . The
mutation frequency was 1 x 10- per pg/al . A dose-dependent increase in DNA adduct
formation was observed for all three cell types . In each case a single major adduct
appeared to be formed . The levels of #dducts at equivalent doses were similar in the
two mammalian cell types (ca . 2 per 10 DNA bases at the 10 pg/al dose) . A comparable
adduct level was observed at 1 yg/ml in the Salmonella calls . Further work to characterize
the DNA adduct formed by !IX is needed to elucidate the role of this lesion in
the genotoxic action of this compound . (This abstract does not necessarily reflect EPA
policy) .
368
MUTAGENS IN CHLORINATED WATER . J .R . Meier, Health Effects Research Laboratory,
U .S . Environmental Protection Agency, Cincinnati, OH 45268
Over the past decade, substantial evidence has accumulated to show the widespread
presence of genotoxins in drinking water . The sources of genotoxic contaminants can
be generally classified into three groups ; contaminants of the raw water, chemicals
added or formed during water treatment, and chemicals formed or unintentionally added
during distribution . In many cases, the genotoxic activity can be directly attributed
to the chlorination stage of water treatment . The genotoxic activity appears to originate
primarily from reactions of chlorine with humic substances in the source waters .
Cenotoxic activity in drinking water concentrates has been most frequently demonstrated
using bacterial mutagenicity tests but results with mammalian cell assays are generally
consistent with the findings from bacterial assays . There is currently no evidence
for genotoxic damage following in vivo exposure, although little work has been done in
this area . Organic acids appear to account for most of the bacterial mutagenicity and
recovery of these compounds from water requires a sample acidification step prior to
extraction . Recently, one class of acid cospounds, the chlorinated hydroxyfuranones,
was found to be responsible for a major part of the mutagenic activity . Approaches
for drinking water treatment aimed at reduction of genotoxins in drinking water include
granular activated carbon (GAC) filtration, chemical destruction, and the use of alternative
means of disinfection (i .e ., ozone, chlorine dioxide, and monochloroamine) .
The question of how best to minimize exposure to genotoxins in drinking water while
maintaining a microbiologically safe water remains to be resolved . (This abstract
does not necessarily reflect EPA policy) .
369
HERITABLE VARIATION IN THE RESPONSE OF A CLINICALLY NORIIAL, AU!tAN POPULATION TO ION-
IZING RADIATION . T . Merz, D .Y . Harrison, L .A . Corey, Medical College of Virginia,
Virginia Commonwealth University, Richmond, VA (USA)
This is a study of the inheritance of variability in the response of clinically
normal individuals to ionizing radiation . The micronucleus assay is used to measure
response and since micronuclei frequencies are dependent on cell proliferation, cell
growth kinetics are also considered . Then twin method is used to determine whether
there is a heritable component of variation in the response of cells from clinically
normal individuals . Ten pairs of monozygotic twins were examined for their responses
to radiation . The variation of the response of twins within a pair is compared
to the variation between pairs of twins . An analysis of variance does indlcate
that there is considerable variation in observed micronuclei frequency . Nost
of the variability can be accounted for by the differences between twin pairs . The
large interpair variation compared to the intrapair variation demonstrates that
twin micronuclei production is more alike (correlation of 0 .92) than non-twins . It
is suggestive of a genetic influence on mlcronuclel production .