Environmental and Molecular Mutagenesis - Legacy Tobacco ...

132 1989 EMS Abstracts
http://legacy.library.ucsf.edu/tid/clb93d00/pdf
Notes Durtng incomplete combustion of organic matter there is a formation of po)ycyclic aromatic
hydrocarbons IPAH) which can react with nitrogenoxides, with the formation of nttro-PAH'a
as a result, a reaction which Is catalyzed by a low ptl . 2-Nitrotluorene (`IF), a marker for nftro-
PAH, is in vivo metabolized via two different routes . After inhalation there ts a formation of
potent mutagenic metabolites . OH-NF's, which are distributed In the body. After oral administration.
NF is reduced to the amine, a reaction mediated by the intestinal mtcrollora . and
further acetylated to 2-acetylaminoAuorene (AAF), a potent carcinogen . Further ringhydroxyladon
of AAF leads to detoxification and excretion .
Induction of cytochrome P450 c .d affects the metabolism tn that more OH-NF'a are formed . As
a consequence, more mutagenic metabolites are found In the circulation . The liver excretes OH-
NF's as . In terms of mutagenictty. , totally harmless glucuronide conjugates . When these
conjugates are excreted via the bUe . Intestinal beta-glucuronidase can liberate direct-acting
mutagens tn the intestine . Thus, inhalation of NF can lead to formation of potent mutagens in
the mtesttne.
NF induces DNA-repair. In vivo, and is an tnttlator and a weak promotor, measured as formation
of preneoplastic lesions in the liver. Risk estlmates, by two different methods . Indicate
that nltro-PAH's, extrapolated from the marker NF. can expose humans to a cancer risk .
380
POINT hlJTATION AND CYTOGENETIC A'MLYSIS OA' L1TiPFDCY7ES FROM NH .RtOCYSTICFtCOTIC PATIFATS
TRFATID WITH PRAZIWANTFL, R . Montero , D . Valencia , F . Moreno *, *f . Sandoval * and
P . Ostrosky-Wegman . Instituto de Investivaciones Riomddicas, U .N.A .N ., Hosnital de
Psnecialidades, Centro MBdico la Raza . Ando . Postal 70228, C .P . 04510, Wxico, n .F .
Evaluation of genotoxic effects of praziouantel on neurocysticercotic piv. lyrtmhocytes
showed an increased frequency of poliploids with res±+ect to non-infected animals and
also a greater suscentibility to clastogenic damaqe . When same study was intented on
humans we met a major problem on choosing adequate controls for neurocysticercotic
patients since they are exnosed to several mutagenic agents before the correct diagnose
is done ; these include com?wtarized axial tanopranhy, anticonvulsants, anesthetics,
antiinflamnatory druqs and antibiotics . Our controls, therefore, include non-infected
persons in one hand and neurocysticercotic natients exoosed to different combinations
of treatments, all of them before they received the nraziauantel treatment, on the
other hand . The terminal noints studied were : structural and numerical chronosomal
aberrations, sister chromatid exchanges, cell cycle kinetics and 6-thiopuanine resistant
lymhocyte frequency . Results show that neurocysticercotic status, which involves
exposure to the agents mentioned, causes retardation on cell cycle kinetics ;
besides, hprt assay results show that in some aatients there is also an increase on
point mutations . After praziquantel treatment it was found that cell cycle kinetics
return to normal values .
THE COMPARISON OF MUTAGEN-INDUCED THYMIDINE KINASE (TK) MUTANT FREQUENCIES IN HUMAN
AND MOUSE LYMPHOMA TESTING CELLS . M .M . Moorel, K . Harrington-Brock2 L . Parker2 .
1U .S . Environmental Protection Agency, Research Triangle Park, NC 27711 USA ;
2Environmental Health Research and Testing, Inc ., Research Triangle Park, NC 27709
USA .
The TK6 line of human lymphoblastoid cells can be used to detect mutants at the
heterozygous thymidine kinas* (1k) locus . Little et al . (1987, Banbury Report 28 :
Mammalian Cell Mutagenesis, p . 225) have reported that a class of slow-growing TK
mutants can be recovered and that at least some of these mutants may result from
mitotic recombination . These results are similar ta our findings for small-colony
TK-deficient mutants of mouse lymphoma cells . We wished to make quantitative
comparisons between the induced mutant frequency in the human and mouse lymphoma
cells . Slow-growing mutants are difficult to recover and count using the procedures
standardly used with the TK6 cell line . We are itnrestigating modifications which
might optimize growth and quantitation of slow-6roving mutants . Modifications
include using 24 well plates rather than 96 well plates and plating cells at 1x103
to 5x103 rather than 4x104 cells per well . Using these procedures, we are comparing
the ICR-170-, EMS-, and MMS-induced TK mutant frequencies in human and mouse
lymphoma cells . (This 1s an abstract of a proposed presentation and does not
necessarily reflect U .S . EPA policy .)
381
382
IN VIVO REPAIR DURING G~ OF GA!!IA RAYS INDUCED LESIONS ELICITING SISTER CHRQIATID E%
CHANGES (SCEs) IN MURINE SALIVARY GLAND CELLS .
Pedro Morales-Ramfrez, Teresita Vallarino-Kelly and Re ina Rodr2 uez-Reyes .
Instituto Nacional de Investigaciones Nucleares, Mgxico, D .F ., I~XICO) .
The in vivo ability of mouse cells to repair gamma radiation induced lesions capable
of eliciting SCEs was examined . The experimental protocol was done in mouse salivary
gland cells induced to parasynchronical division by isoproterenol (1 umole/gm bd
wt) . Two groups of mice were irradiated with 0 .38 Gy in a 6OCo source (Vick Rad) at a
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