Environmental and Molecular Mutagenesis - Legacy Tobacco ...

306 1989 EMS Abstracts
TFLE USE OF EGDCTORATE FOR M7NITDRING oCCUPATIQQ L P70?OBURE
Notes
A . Krmkje, Department of Botany, The University of Trondheim, Norway
The aim was to investigate if mutagens are biologically available . The workplace
investigated is the top of the batteries in a coke plant, where relatively high
concentrations of polycyclic arrnwtic hydrocarbons (PAHs) are usually measured in the
air. The study is aimed at group exposure . The 4 groups studied are control nonsmkers,
control smokers, battery naumnkers and battery smoke.rs . The workers gave their samples
within half an hour of finishing the workshift and after the night's sleep - "morning
expectorate" . The samples from each group were pooled, hydrolysed with alkaline
methanol and extracted with cyclohexane . The S . typhitturium strains TA98 and TA100
rx:re used in the Salmonella/micro®ane-test . Liver and lung hanogenates were used as
metabolic activation systems . The expectorate fran exposed workers - mostly fran
smokers, but also to a certain extent fran nonsmkexs - were mutagenic ; however, the
control samples fran both smokers and nonamokers were not . The positive results
produced by expectorate samples from the exposed smokers suggest a synergistic
relationship between exposure to air pollution of the working attrosphere and smoking .
The analysis of the "morning expectorate" shnws that inhaled pollution with potential
nrtagens is not effectively removed from the respiratory system during the night . The
salmonella-test used on expectorate samples may be an effective assay in certain types
of industries, viz . where the atmsphere contains partieulates acting as carriers for
mutagens apt to be eluated by the body fluids or cellular membranes .
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BACTERIAL MUTAGENICITY ASSESSMENT OF STRUCTURALLY-RELATED QUINOLINE
THIAZOLAMINE COMPOUNDS, POTENTIAL ANTIPSYCHOTIC DRUGS . M .L . Kropko, J .C .
Jaen, S .A . Wold, B .W . Caprathe, L.D . Wise, and J .C . Theiss, Parke-Davis Pharm .
Res . Div ., Warner-Lambert Co ., Ann Arbor, MI(USA)
Quinoline thiazolamines have potential for antipsychotic activity . In a
routine Ames assay (TA98, TA100, TA1S35, TA1537, TA153B, S9t), PD 123403 was
found to be mutagenic to TA98 (peak response of 14-fold background at 32
ug/plate) and TA1538 (peak response of 19-fold background at 100 ug/plate)
in the presence of S9 only . This frameshift mutagen is a quinoline
thiazolamine comprised of fused pyridine, cyclohexane and aminothiazole rings .
To provide structure-activity information for development of a non-mutagenic
antipsychotic drug in this chemical class, structural analogs were synthesized
and screened for mutagenicity using TA1538 with S9 . Methylation of the
cyclohexane ring gave a weak mutagen (peak response of t .4-fold background at
316 ug/plate) . Mutagenic activity was completely lost (maximum dose tested of
10,000 ug/plate) either upon removal of the amine from the aminothiazole ring,
upon ethyl substitution of the nitrogen in the partially reduced pyridine
ring, upon saturation of the pyridine ring with hydrogen, or upon
removal of the cyclohexane ring . These results suggest that oxidation of
PD123403 by S9 may take place at the cyclohexane ring, producing a mutagenic
fully aromatic amine compound . Thus, modifications to this quinoline
thiazolamine which prevent oxidation to a tricyclic heteroaromatic amine,
while at the same time not interfering with pharmacological activity, should
result in a non-mutagenic antipsychotic .
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TOXICITY OF ENDRIN ( A CHLORINATED HYDROCARBON ) ON THYROID HORMONE
FORMATION OF A TELEOST . DHYANENDRA KUMAR,Department of Zoology,Jagjiwan
College,Magadh University, ARRAH,Bihar,INDIA .
Hypofunction of thyroid due to environmental pollutants may be mediated
through the inhibition of thyroid peroxidase enzyme as this enzyme from
pronephric (head) kidney and pharyngeal sources is readily inactivated
by pesticides . Environmental pollutants such as organochlorine and
carbondisulphide considerably depress thyroid function in fish .
5'lhen Anbas testudineus,Bloch (a teleest) was exposed to 48 hr TLM
concentration (0 .05 ppm ) of endrin, formation of MIT (Monoiodotyrosine)
and ,IT (Diiodotyrosine) by head kidney soluble supernatatnt fraction
were markedly depressed . Foemation of T(Thyroxine) was found to be
similarly inhibited due,to endrin pollution . Per cent of inhibition
due to exposure of 48 hr TLM to endrin was found to De 53 .6,56 .06 and
50 .4'; for the formation of MIT,DIT and T4 respectively . Inhitory
effect of endrin could effectively reversed by Cytochrome c .
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