Environmental and Molecular Mutagenesis - Legacy Tobacco ...

530 ©
GENOTOXICITY EVALUATION OF CHLORTETRACYCLINE
R .K . Sharma, K .A . Traul,-C . Caterson, J . Harbell, A . Thilagar, D . Putnam, American
Cyanamid Co ., Princeton,~--NJ ; Sitek Research Labs ., Rockville, MD ; Microbiological
Associates, Bethesda, MD .
Chlortetracycline-HC1 (CTC-HC1), a broad-spectrum antibiotic, was tested in a
battery of short term j.D vitro (microbial and mammalian point mutation, and
unscheduled DNA synthesis) and JjI y.jy4 (rat bone marrow chromosome aberrations)
tests . Microbial and mammalian point mutation testing was done with and without rat
S9 metabolic activation ; all tests had concurrent positive and negative controls . The
microbial mutagenesis assay .jn J . tyohi~yyrium and E . Sg]j was conducted up to a dose
of 10 pg/plate, in the presence and absence of S9, limited by toxicity . No increase
in revertants per plate was observed . In the CHO/HGPRT mammalian gene mutation assay,
doses (based on solubility and cytotoxicity) of 100,80,60,40 and 20 pg/ml (+S9) and
125,100,75,50, and 25 pg/ml (-S9) were found to be nonmutagenic . In the rat (Sprague
Dawley) bone marrow cyto enetic test, CTC-HC1 was administered by oral gavage at
5,000, 2,500, and 500 mgYkg in males and females, based on a range-finding study .
Bone marrow was harvested at 12,24 and 36 hours after treatment . CTC-HCl induced no
increases in chromosomal aberrations in either sex at any dose or time point . In the
rat hepatocyte primary culture/DNA repair (UDS) test, doses tested ranged from 25 to
75 pg/ml, limited by cytotoxicity . None of the doses produced a mean grain count of
more than five compared to vehicle control . Positive controls in each test system
produced significant positive responses . It is concluded that Chlortetracycline-HC1
is not mutagenic in these test systems .
531
GENOTOXICITY EVALUATION OF SULFAMETHAZINE
R .K . Sharma, K .A . Traul, C . Caterson, E . Johnson, R .R . Young, J .L . Ivett . American
Cyanamid Co ., Princeton, NJ ; Hazleton Laboratories America, Inc ., Kensington, MD .
Sulfamethazine (SULMET), a bacteriostatic antibiotic, was evaluated for genotoxic
potential in a battery of short term j,n yitro (microbial and mammalian point
mutation) and jIl yjys (rat bone marrow chromosome aberrations) tests . Microbial and
mammalian point mutation testing was done in the absence and presence of rat S9
metabolic activation ; all tests had concurrent positive and negative contro)s .
The microbial mutagenesis assay in a . tvohimurium and F . & Q]j was conducted up to a
dose of 10 µg/plate, in the presence and absence of S9, limited by toxicity . No
increase in revertants per plate was observed . In the CHO/HGPRT mammalian gene
mutation assay, doses (based on solubility and cyto~oxicity) ranging from 0 .5 to
7 .0 mg/ml with and without metabolic activation, were found to be nonmutagenic . In
the rat (Sprague Dawley) bone marrow cytogenetic test, SULMET was administered by
oral gavage at 3,000, 1,500, and 750 mg/kg in males and females, based on a rangefinding
study . Bone marrow was harvested at 6, 18 and 30 hours after treatment .
SULMET induced no increases in percentages of chromosomally aberrant cells or in the
frequency of aberrations per cell per animal in either sex at any dose or time point .
Positive controls in each test system produced significant positive responses . It is
concluded that Sulfamethazine is not mutagenic in these test systems .
532
MONITORING THYMIDINE CATABOLISM IN COMPLEX NATURAL SYSTEMS : A SIMPLE, NOVEL METHOD
FOR ECOTOXICITY ASSESSMENT
T . Shaw, D .G . MacPhee 6 R.H . Smillie*, Departments of Microbiology, La Trobe
University and Biochemiatry, University of Melbourne* (Australia)
Thymidine is one of the most important molecules in biology . Numerous bioassays
depend on measurement of incorporation of radiolabelled thymidine into acid-insoluble
macromolecules, usually presumed - often without justification - to be DNA . In the
majority of steady-state biological systems, and in particular in natural ecosystems
where cell growth and turnover are slow, thymidine catabolism and incorporation into
non-DNA macromolecules is almost invariably quantitatively more important than its
anabolism and incorporation into DNA . Consequently, we investigated the influence
of toxic compounds on thymidine catabolism in various biological systems . Our work
demonstrates that (1) meaeurement of thymidine catabolism is extremely simple even
in complex systems, because at saturating concentrations of exogenous thymidine, its
catabolites diffuse into the extracellular environment at a faster rate than they can
be re-utilised, and (2) that in stable aquatic microenvironments, the rate of catabolism
of exogenously supplied thymidine is influenced in a time- and dose-dependent
fashion by an enormous variety of compounds including "classical" cytotoxins and
genotoxins, as well as other compounds not usually considered to be in either of these
categories . We conclude that monitoring thymidine catabolism yields useful information
about the metabolic state of all systems investigated and seems to show great
potential as an indicator of toxicity .
http://legacy.library.ucsf.edu/tid/clb93d00/pdf
1989 EMS Abstracts 183
Notes