Environmental and Molecular Mutagenesis - Legacy Tobacco ...

1989 EMS Abstracts
at the later time points . Relative cloning ability was determined by exposing P3 Notes
cells to concentrations of 0 .1 to 1 .0 VM BRdU or CLdU for 7 days . Each toxicant
reduced cloning ability from 100% to less than 1%, although CLdU was more efficient on
a concentration basis than BRdU . Not only were the toxic effects of CLdU greater than
those of BRdU, but also its ability to perturb the cell-cycle .
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INSECTICIDES AND CAF2CZNOGQI METAHOLIZING ENZYMES
M .H . MU6'i'AFA AND A .H . Etrlt(%aEIDY . Institue of Graduate Studies and Research,
Alria University, alexandria, Egypt .
The effect of various insecticides on the activities of sane carcirtgertntt:tabolizing
enzymes and the eytocliratr` P-450 of rat liver microsomes were studied . Organoc.hlorine
insecticides, Lindane, DDT and Endrin significantly increased the activity
of arylhydrocarbon hydroxylase (AHH) . Pretreatment of rats with the synthetic pyrethroids,
fenvalerate insignificantly increased the enzyme activity . Pretreatment with
carbaryl, a carbamate derivative and Ditnethoate, an orgartophosphrotls oatQottrd did not
affect the AHH activity . Our data showed that all the tested insecticides which altered
the AHH activity have similar effect on tht: cy''.,ochrane P-450 oontent . The data revw
ealed the ability of various insecticides to increase the atsotlrtt of cytochrattta P-450
and the AHH activity which ttssy increase the nutagenic and carcinogenic activity of
benzo-a-pyrene, since such an activity is dependent an the induction of cytocYurome
P-450 dependent AHH . A second enzyme was also investigated, dintethylnitrosamine (DM4)
demethylase I and II . Pretreatntutt of rats with Lindane, DDT and Endrin decreased the
activity of Dm-demethylase I and increased the activity of DMN-danethylase II .
Fenvalerate and carbamate pretreatment groduoed insignificant change an both enzymes .
Pretreatment with Dimethoate inhibited the oxidative N-darethylaticn of DMD1 . Since
the metabolism of carcinogens by cytochrrnie P-450 dependent mx0aager>ares often
facilitates their elimination or activiation, alteration of norntal tuetabolicpn t2xaays
of these carcinogens by various insecticides may alter the intensity and duratiort or
action of these environmental carcinogens .
390
GE\OTOXIC POTENTIALITIES OF ::-NITRU-METIOXYNAP T8O ('2,1-b) FURAN (R 7000)
IN RELATION TO Ti{E GENERAL PROBLEM .
J . Moutschen, J . Gilot-Delhalle, M . Moutschen-Dahmen, and F . London,
University of Liige, Sart-Tilman 1322, D-4000 Liege (BELGIUM)
Mutagenic activity of R'7000 was tested on two strains of Sehizoe? ccharomyces
pombe ade 7 and ade 6 (at doses ranging from 0 .0Gto 32 . .0 M) .
It was different in both strains . R 7000 showed clastogeniciSy in Nigella
damascena chromosomes at doses ranging from 0 . 12 to 32 .t0-5M for seeds
and 0 . 12 to 2 .10-5M for root tips . Treatments of dry seeds revealed the
sensitivity of GO whereas treatments of presoaked seeds showed the aensivity
of Gl, S and G': . These results were confirmed by treatments of
growing root tips with a much higher sensitivity of the later phases of
the mitotic cycle . These treatments yielded a high amount of gaps (G'and
G") . The results are in agreement with those obtained after treatments
of animal cells . Additionally, some treatments induced strong stathmokinetic
effects analysed in details . The spectrum of induced chromosome
damage shows similarities with the spectrum of lesions induced by cytosine-arabinoside
and other related substances, wich suggests some mechanisms
of action . In conclusion, R 7000 belongs to the class of substan-,
ces with multiple genotoxic effects, and its position in the important
class of furans has to be revaluated .
391
AN SAR STUDY OF THE MUTAGENICITY OF PAH COMPOUNDS IN SALMONELLA
TYPHIMURIUM . Susan R . Moyer and Peter C . Jurs, Chemistry Department, Penn State University,
University Park PA 16802
Many Polycyclic Aromatic Hydrocarbons and their derivatives have been shown to be potent
mutagens in Salmonella ryphirnuritun via the Ames test . A group of 110 PAHs (48 active and 64
inactive) were obtained from the literature and were used to carry out a structure-activity relationship
study. All of the compounds were tested by LaVoie and coworkers using S . ryphimtvitun TA100 with
metabolic activation . The molecular structures were entered into the ADAPT software system by
sketching them on a computer terminal . Three-dimensional molecular models were constructed using
molecular mechanics . Then, topological, geometrical, and electronic molecular structure descriptors
were calculated for each compound . Specific structural features were encoded by using substructure-
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