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Environmental and Molecular Mutagenesis - Legacy Tobacco ...

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8 1989 EMS Abstracts<br />

Notes led to the hypothesis that proliferating rather then "resting" T-lyaphocytes are<br />

preferentially susceptible to gsne mutations in vivo . This may have significant<br />

implications for interpreting human in vivo mutagenicity studies . Research supported by<br />

NCI CA30688 <strong>and</strong> DOE FG0287ER60502 .<br />

http://legacy.library.ucsf.edu/tid/clb93d00/pdf<br />

INFLUENCE OF DIFFERENT FACTORS ON THE INDUCTION or KALSEGREGATION IN<br />

SACCHAROMYCES CEREVISIAE D61 .M BY BAVISTAN .<br />

Silvio Albertini, Pharmaceutical Research, Department of Toxicology,<br />

F .Hoffmann-La Roche o Co ., Ltd, CH-4002 Basel, Switzerl<strong>and</strong> .<br />

Bavistan is known as a potent inducer of malsegregation in Sacharom ces<br />

cerevisiae . with both st<strong>and</strong>ard protocols used with S . cerev s ae D .M<br />

overnight incubation <strong>and</strong> cold treatment protocol, respectively)<br />

bavistan induced malsegregants in the same range . The frequencies obtained<br />

were not influenced by the plating volume used on selective medium<br />

. The higher the YEP content the more distinct the toxicity <strong>and</strong> the<br />

induction of malsegregants was . The physiological temperature for<br />

yeasts of 28°C led to a more pronounced induction than 33°C <strong>and</strong> 37°C . A<br />

clear observable induction by bavistan was detectable after 8 hours<br />

incubation (overnight protocol) <strong>and</strong> 1 .5 hours of the second incubation<br />

period (cold treatment protocol), respectively .<br />

Comparison of the growth of mixed cultures of red, cycloheximide<br />

sensitive cells <strong>and</strong> white, cycloheximide resistant, leucine auxotrophic<br />

cells prepared at different ratios revealed, that there is a strong<br />

selection towards red cells <strong>and</strong> against the malsegregants .<br />

PLASKID COPY NUMBER AND MUTANT FREQUENCIES IN S .TYPHIMURIUM TA102<br />

Silvio Albertini <strong>and</strong> Elmar Gocke, Pharmaceutical Research, Department<br />

o Tox co ogy, c .Hoffmann-La Roche i Co . Ltd, CH-4002 Basel,Switserl<strong>and</strong> .<br />

Tetracycline <strong>and</strong> chloramphenicol increase the number of mutant colonies<br />

of strain TA102, which carries the reverting gene on the plasmid pAQl .<br />

Determination of the plasmid content by agarose gel analysis shows that<br />

the increase of the mutant colony number is paralleled closely by an<br />

increase of the number of pAQl plasmids per cell, indicating that the<br />

two compounds do not increase the frequency of mutants "per gene", but<br />

only enhance the number of genes at which mutations can occur . Thus,<br />

not considering the molecular processes could result in mistakenly<br />

attributing the increase in the number of mutants per plate (respective<br />

to the number of mutants per cell) to a mutagenic activity of the antibiotics<br />

. An other antibiotic, kanamycin, acts by reducing the translation<br />

fidelity which leads to read through of the ochre stop codon <strong>and</strong><br />

thereby to an accumulation of enough functional enzyme so that enhanced<br />

cellular growth is possible .<br />

These different mechanisms all mimic mutagenic responses with some<br />

analogies to the effect of growth enhancing compounds (e .g . complex<br />

mixtures containing histidine) . It is discussed whether such false<br />

positive results are likely to occur in routine testing with TA102 <strong>and</strong><br />

how to avoid possible misinterpretation .<br />

17<br />

INDIRECT EFFECT OF SOME DNA DAMAGING AGENTS ON LAMBDA RECOMBINATION . D . Alcintara-Dfaz<br />

<strong>and</strong> N . Brefia-Valle, Instituto Nacional de lnvsstigaciones Nucleares, Kixico, D .F . (NE-<br />

IQCO) .<br />

Recombinant progeny of undamaged lambda phage, increases up to four times when infecting<br />

E . coli hosts previously irradiated with UV light. A similar effect occurs in<br />

the mutant recA-441 (tif-1) SOS induced by hest, but so far none could be detected in<br />

lexA (ind-) bacteria (Alcfintara <strong>and</strong> BreBa, data submitted for publicatioa) . All these<br />

results suggeat an SOS-dependent stimulation of undamaged lambda recombination . The<br />

present work shows more data supporting the former view . Phage crosses were carried<br />

out according to st<strong>and</strong>ard procedures in hosts with distinct repair capabilities treated<br />

with either UV or three other genotoxicants . An increase of 7 times the normal recombinant<br />

progeny was found in umuC cells exposed to 50 J/m2 of W light, a fact which<br />

to our view proves that these ara true recombinants <strong>and</strong> not mutants due to the well<br />

known W effect . On the other h<strong>and</strong> the experiments using FRlC, l04S <strong>and</strong> MJNG as recombina<br />

tion stimulants show that whereas no affect could be found in treated E . coli lexA<br />

(ind-) hosts, a significant increase in phage recombinaits occurred whan Tnfecting<br />

15<br />

16

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