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Title
Modulation of Masheri- and benzo[a pyrene-inducible
carcinogen-metabolizing enzymes by dietary vitamin A.
Author
Ammigan N; Nair UJ; Bhide SV
Address
Carcinogenesis Division' Tata Memorial Centre' Parel' Bombay'
India.
Source
Biochem Med Metab Biol, 44(2):181-91 1990 Oct
Abstract
The modulatory role of dietary vitamin A on the carcinogen metabolizing
enzymes was studied in masheri extract and benzo[a pyrene-treated
rats.
Weanling male Sprague-Dawley rats were fed vitamin A deficient
(SR-)
and vitamin A sufficient (SR+) semisynthetic diets for 12 weeks.
ME/B[a
P treatment significantly increased the phase I activating enzymes
in
both SR- and SR+ groups. However' a higher percentage increase
in
enzyme activities was observed in both liver and lung of the
SR-
animals compared to the SR+ groups. glutathione content and activity
of
glutathione S-transferase were decreased in both liver and lung
of SR-
animals on treatment with either ME or B[a P. In the SR+ group'
an
increase in GSH content and GST activity was observed following
the
ME/B[a P treatment. The hepatic pool of vitamin A was depleted
while
that of vitamin C was increased after ME or B[a P treatment in
both SR-
and SR+ groups.
Title
Carcinogen metabolism and DNA adducts in human lung tissues as
affected
by tobacco smoking or metabolic phenotype: a case-control study
on lung
cancer patients.
Author
Bartsch H; Petruzzelli S; De Flora S; Hietanen E; Camus AM; Castegnaro
M; Geneste O; Camoirano A; Saracci R; Giuntini C
Address
International Agency for Research on Cancer' Lyon' France.
Source
Mutat Res, 250(1-2):103-14 1991 Sep-Oct
Abstract
Individual variations in activity of pulmonary enzymes that metabolize
tobacco-derived carcinogens may affect an individual`s cancer
risk from
cigarette smoking. To investigate whether some of these enzymes
(e.g.'
cytochrome P450IA-related) can serve as markers for carcinogen-induced
DNA damage accumulating in the lungs of smokers' non-tumorous
lung
tissue specimens were taken during surgery from middle-aged men
with
either lung cancer (n = 54) or non-neoplastic lung disease (n
= 20).
Phase I (AHH' ECDE) and phase II (EH' UDPGT' GST) enzyme activities'
glutathione and malondialdehyde contents were determined in lung
parenchyma and/or bronchial tissues; some samples were analyzed
for DNA
adducts' using 32P-postlabeling. Data analysis of subsets or
the whole
group of patients yielded the following results. (1) Phase I
and II
drug-metabolizing enzyme (AHH' EH' UDPGT' GST) activities in
histologically normal surgical specimens of lung parenchyma were
correlated with the respective enzyme activities in bronchial
tissues
of the same subJect. (2) In lung parenchyma' enzyme (AHH' ECDE'
EH'
UDPGT) activities were significantly and positively related to
each
other' implying a similar regulatory control of their expression.
(3)
Mean activities of pulmonary enzymes (AHH' ECDE) were significantly
(2-
and 7-fold' respectively) higher in lung cancer patients who
had smoked
within 30 days before surgery (except GST' which was depressed)
than in
cancer-free subJects with a similar smoking history. (4) In the
cancer
patients' the time required for AHH' EH and UDPGT activities
to return
to the level found in non-smoking subJects was several weeks.
(5)
Bronchial tree and peripheral lung parenchyma preparations exhibited
a
poor efficiency in activating promutagens to bacterial mutagens
in
Salmonella. However' they decreased the mutagenicity of several
direct-acting mutagens' an effect which was more pronounced in
tissue
from recent smokers. GSH concentration and GST activity were
positively
correlated with mutagen inactivation in the same sample. (6)
In recent
smokers' AHH activity in lung parenchyma was positively correlated
with
the level of tobacco smoke-derived DNA adducts. (7) Pulmonary
AHH and
EH activity had prognostic value in tobacco-related lung cancer
patients. (8) An enhanced level of pro-oxidant state in the lungs
was
associated with recent cigarette smoking. Malondialdehyde level
in lung
parenchyma was associated with the degree of small airway obstruction'
suggesting a common free radical-mediated pathway for both lung
cancer
induction and small airway obstruction.(ABSTRACT TRUNCATED AT
250
WORDS)
Title
The effect of mainstream and sidestream cigarette smoke exposure
on
oxygen defense mechanisms of guinea pig erythrocytes.
Author
MukherJee S; Woods L; Weston Z; Williams AB; Das SK
Address
Department of Biochemistry' Meharry Medical College' Nashville'
TN
37208
Source
J Biochem Toxicol, 8(3):119-25 1993 Sep
Abstract
We have studied the effects of short-term exposure of guinea
pigs to
cigarette smoke under both mainstream (MS) and sidestream (SS)
conditions on the activities of maJor antioxidant enzymes and
lipid
peroxidation potential of erythrocytes. The smoke-exposed groups
had an
increase in the activity of superoxide dismutase (SOD)' a decrease
in
the activities of glutathione peroxidase (GSH-Px) and NADPH generating
enzymes' and no change in the activity of catalase. Furthermore'
there
was a significant increase in the in vitro lipid peroxidation
potential
of erythrocytes in both MS- and SS-exposed groups. However' the
lipid
peroxidation potential was higher in the MS-exposed group than
that in
the SS-exposed group.
Title
Modification of plasma proteins by cigarette smoke as measured
by
protein carbonyl formation.
Author
Reznick AZ; Cross CE; Hu ML; Suzuki YJ; KhwaJa S; Safadi A; Motchnik
PA; Packer L; Halliwell B
Address
Membrane Bioenergetics Group' University of California' Berkeley
94720.
Source
Biochem J, 286 ( Pt 2)():607-11 1992 Sep 1
Abstract
Exposure of human plasma to gas-phase (but not to whole) cigarette
smoke (CS) produces oxidative damage to lipids [Frei' Forte'
Ames &
Cross (1991) Biochem. J. 277' 133-138 ' which is prevented by
ascorbic
acid. The ability of CS to induce protein damage was measured
by the
carbonyl assay and by loss of enzyme activity and protein -SH
groups.
Both whole and gas-phase CS caused formation of carbonyls in
human
plasma' which was partially inhibited by GSH but not by ascorbic
acid
or metal-ion-chelating agents. Isolated albumin exposed to CS
showed
much faster carbonyl formation (per unit protein) than did whole
plasma; damage to isolated albumin was partially prevented by
chelating
agents. Isolated creatine kinase (CK) lost activity upon exposure
to CS
much faster than did CK in plasma. Direct addition to plasma
of
mixtures of some or all of the aldehydes reported to be present
in CS
caused protein carbonyl formation and inactivation of CK' but
neither
occurred to the extent produced by CS exposure.
Title
Coordinated activation of as-1-type elements and a tobacco glutathione
S-transferase gene by auxins' salicylic acid' methyl-Jasmonate
and
hydrogen peroxide.
Author
Xiang C; Miao ZH; Lam E
Address
AgBiotech Center' Rutgers University' New Brunswick' NJ 08903-0231'
USA.
Source
Plant Mol Biol, 32(3):415-26 1996 Nov
Abstract
The molecular mechanism of signal transduction pathways which
mediate
the action of phytohormones are poorly understood. Recently'
we and
others have shown that the as -1 type cis-acting elements can
respond
to auxin and salicylic acid' two well-characterized signaling
molecules
in plants. In the present work' we have examined a comprehensive
set of
physiological and abiotic agents and found that auxin' salicylic
acid
and methyl-Jasmonate are three effective inducers of the as-1-type
elements in transgenic tobacco. Using a cell suspension culture
containing a synthetic promoter-GUS fusion' we demonstrated rapid
and
sensitive induction of the as-1-type element by these phytohormones.
Furthermore' a tobacco glutathione S-transferase gene' GNT35'
that
contains an as-1-type binding site in its promoter is also inducible
by
auxin' salicylic acid and methyl-Jasmonate with similar kinetics.
As
Ulmasov et al. have recently reported' we found that the as-1-type
elements can also respond to weak/inactive analogues of auxin
and
salicylic acid. In addition' we show that hydrogen peroxide can
also
effectively activate the expression of GNT35 as well as the as-1-type
element in a cell suspension culture' but not with whole seedlings.
These results are discussed with respect to the possible mechanism(s)
through which a single cis element may respond to a diverse array
of
molecules.
Title
Promoter analysis of the auxin-regulated tobacco glutathione
S-transferase genes Nt103-1 and Nt103-35.
Author
Droog F; Spek A; van der Kooy A; de Ruyter A; Hoge H; Libbenga
K;
Hooykaas P; van der Zaal B
Address
Institute of Molecular Plant Sciences' Leiden University' Clusius
Laboratory' Netherlands.
Source
Plant Mol Biol, 29(3):413-29 1995 Nov
Abstract
We have analysed the promoter regions of two closely related
auxin-regulated glutathione S-transferase genes. All active deletion
constructs tested showed expression of the reporter gene
beta-glucuronidase (gusA) in root tips of young seedlings and
newly
developing lateral roots. Auxin treatment greatly enhanced the
level of
expression. The Nt103-1 promoter region -370/-276 was found to
be
necessary' at least as a quantitative element to confer
auxin-responsiveness to a reporter gene' and sequences responsible
for
the auxin-responsiveness must be located downstream of -370.
The region
-651/-370 contains sequence information necessary for uninduced
expression. The Nt103-35 promoter manifested its auxin-responsiveness
within the -504/-310 region. Electrophoretic mobility shift analysis'
using nuclear extracts from tobacco leaves and suspension cells'
identified a factor binding to a sequence (ap103' TGAGTCT) at
position
-560 of the Nt103-1 promoter' which shows homology to the mammalian
AP-1 site. A second factor was found to bind a sequence (as103'
ATAGCTAAGTGCTTACG) with homology to the CaMV 35S promoter as-1
element.
The as103 element is present in both promoters and positioned
around
-360' so within the region determined to be indispensable for
the
response to auxin. A third factor was found binding to the -276/-190
region of both promoters. Combined' these data point to the relevance
of a 90 bp region for auxin-induced activity of both tobacco
genes. The
ASF-1 like factor binding to the as103 element within this region
might
be involved in mediating the auxin response.
Title
Proteins encoded by an auxin-regulated gene family of tobacco
share
limited but significant homology with glutathione S-transferases
and
one member indeed shows in vitro GST activity.
Author
Droog FN; Hooykaas PJ; Libbenga KR; van der Zaal EJ
Address
Institute of Molecular Plant Sciences' Leiden University' Clusius
Laboratory' Leiden' Netherlands.
Source
Plant Mol Biol, 21(6):965-72 1993 Mar
Abstract
A number of cDNAs corresponding to auxin-regulated mRNAs have
been
isolated from tobacco and found to be encoded by a multigene
family
consisting of three subfamilies. Homologous proteins have been
isolated
independently from soybean and potato. Here we report that the
encoded
proteins show a limited but significant homology to both plant
and
animal glutathione S-transferases (GST' EC 2.5.1.18). For the
protein
NT103' encoded by a member of the Nt103 subfamily' we demonstrate
an in
vitro GST activity. This is the first time a function is attributed
to
a member of this group of auxin-induced proteins or any of its
homologues. The implications of this finding and the possible
relationships between auxins and GSTs are discussed.
Title
Overexpression of glutathione S-transferase/glutathione peroxidase
enhances the growth of transgenic tobacco seedlings during stress.
Author
Roxas VP; Smith RK Jr; Allen ER; Allen RD
Address
Department of Plant and Soil Sciences, Texas Tech University,
Lubbock
79409-3131, USA.
Source
Nat Biotechnol, 15(10):988-91 1997 Oct
Abstract
Transgenic tobacco seedlings that overexpress a cDNA encoding
an enzyme
with both glutathione S-transferase (GST) and glutathione peroxidase
(GPX) activity had GST- and GPX-specific activities approximately
twofold higher than wild-type seedlings. These GST/GPX overexpressing
seedlings grew significantly faster than control seedlings when
exposed
to chilling or salt stress. During chilling stress, levels of
oxidized
glutathione (GSSG) were significantly higher in transgenic seedlings
than in wild-types. Growth of wild-type seedlings was accelerated
by
treatment with GSSG, while treatment with reduced glutathione
or other
sulfhydryl-reducing agents inhibited growth. Therefore, overexpression
of GST/GPX can stimulate seedling growth under chilling and salt
stress, and this effect could be caused by oxidation of the glutathione
pool.
Title
Cloning and characterisation of glutathione reductase cDNAs and
identification of two genes encoding the tobacco enzyme.
Author
Creissen GP; Mullineaux PM
Address
Department of Applied Genetics' John Innes Centre' Norwich Research
Park' Colney' UK.
Source
Planta, 197(2):422-5 1995
Abstract
We have isolated 4 cDNA clones (GRT1-4) encoding glutathione
reductase
(GR) from a tobacco (Nicotiana tabacum L.) leaf cDNA library.
The cDNAs
were almost identical: GRT1' GRT3 and GRT4 represented the same
gene'
differing only in that GRT4 contained an intron within the C-terminal
part of the coding sequence. Failure to splice out this intron
resulted
in a substitution of the final 13 amino acids of the deduced
amino acid
sequence. A second gene was represented by GRT2. Southern blots
indicated that there were two related GR genes in tobacco. The
presence
of multiple isoforms of GR in tobacco may be explained in part
by the
expression of a small gene family. In addition' alternative isoforms
may result from translation of different mRNAs derived from the
same
gene by intron skipping during the splicing of nascent GR mRNAs.
Title
Simultaneous targeting of pea glutathione reductase and of a
bacterial
fusion protein to chloroplasts and mitochondria in transgenic
tobacco.
Author
Creissen G; Reynolds H; Xue Y; Mullineaux P
Address
John Innes Centre' Norwich Research Park' Colney' Norwich' UK.
Source
Plant J, 8(2):167-75 1995 Aug
Abstract
N-terminal presequences from cDNAs encoding mitochondrion- or
chloroplast-specific proteins are able' with variable efficiencies'
to
target preproteins to their respective organelles. In the few
cases
studied in which a nuclear-encoded protein is found in both these
organelles' each compartment-specific isoform is encoded by a
separate
gene. glutathione reductase (GR) from peas is encoded by a single
nuclear gene and yet GR is distributed between chloroplasts'
mitochondria and the cytosol. Previous sequence analysis of a
full-length GR cDNA revealed the presence of a putative plastid
transit
peptide. However' expression of this cDNA in transgenic tobacco
resulted in substantially elevated GR activities in both chloroplasts
and mitochondria in four independent lines examined. There was
no
effect on expression of the endogenous tobacco GR genes. Replacement
of
the GR presequence with presequences from pea rbcS (chloroplast)
and
Nicotiana plumbaginifolia Mn-SOD (mitochondrion) resulted in
targeting
of GR only into the appropriate organelle. Expression of a fusion
protein between the amino terminal region of GR and phosphinothricin
acetyl transferase resulted in targeting of the foreign protein
to
chloroplasts and mitochondria. Thus' the pea GR presequence is
capable
of co-targeting this enzyme or a foreign protein to chloroplasts
and
mitochondria in vivo. This is the first example of co-targeting
by a
higher plant preprotein.
Title
Effect of probucol' an oral hypocholesterolaemic agent' on acute
tobacco smoke inhalation in rats.
Author
Ishizaki T; Kishi Y; Sasaki F; Ameshima S; Nakai T; Miyabo S
Address
Department of Internal Medicine' Fukui Medical School' Japan.
Source
Clin Sci (Colch), 90(6):517-23 1996 Jun
Abstract
1. We hypothesized that probucol' an oral hypocholesterolaemic
agent'
can suppress the oxidant stress induced by acute tobacco smoke
inhalation in rats. We determined lung tissue glutathione (reduced
and
oxidized)' lipid peroxide' tocopherol and plasma elastase inhibitory
capacity' ferroxidase activity and lipid peroxide in rats after
inhalation of tobacco smoke. 2. Rats treated with the probucol
diet for
3 days or 4 weeks equally showed no suppression of plasma elastase
inhibitory capacity and ferroxidase activity compared with control
rats
after acute tobacco smoke inhalation' although both animals treated
with probucol for 3 days or 4 weeks had pharmacologically effective
concentrations of probucol to lower plasma cholesterol but plasma
cholesterol in rats treated with probucol for 3 days was still
in the
normal range. 3. Probucol treatment for 4 weeks lessened tobacco
smoke-induced suppression of lung tissue glutathione' attenuated
tobacco smoke-induced increases in lung tissue lipid peroxide
and did
not alter lung tissue tocopherol compared with control (lungs).
4.
These findings demonstrate that probucol' via its antioxidant
ability'
confers a protective effect on lung exposed to acute tobacco
smoke
inhalation.
Title
Larynx cancer risk in relation to glutathione S-transferase M1
and T1
genotypes and tobacco smoking.
Author
Jourenkova N; Reinikainen M; Bouchardy C; Dayer P; Benhamou S;
Hirvonen A
Address
Unit of Cancer Epidemiology (INSERM U351), Institut Gustave-Roussy,
Villejuif, France.
Source
Cancer Epidemiol Biomarkers Prev, 7(1):19-23 1998 Jan
Abstract
glutathione S-transferase (GST) isoenzymes are involved in the
detoxification of several tobacco smoke-derived carcinogens.
It is thus
conceivable that deficiency in GST activity due to homozygous
deletion
of the GSTM1 and GSTT1 genes (the null genotypes) may modulate
susceptibility to smoking-induced cancers. The effects of the
GSTM1 and
GSTT1 null genotypes on laryngeal cancer risk were evaluated
using
peripheral blood DNA from 129 larynx cancer patients and 172
noncancer
controls, all of whom were regular smokers. Increased larynx
cancer
risk was related to the GSTM1 null genotype [odds ratio (OR)
= 1.6, 95%
confidence interval (CI) = 1.0-2.8 . The OR associated with the
GSTT1
null genotype was increased, although not significantly (OR =
1.4, 95%
CI = 0.7-2.9). Individuals with concurrent lack of GSTM1 and
GSTT1
genes had a doubled, although not significant, risk for larynx
cancer
when compared with those having at least one of these genes (OR
= 2.0,
95% CI = 0.8-5.2) and had almost a 3-fold risk (OR = 2.7, 95%
CI =
1.0-7.4) when compared with those with both genes. Moreover,
a
significant interaction between the GSTM1 genotype and levels
of
tobacco consumption (P < 0.05) was found; the GSTM1 null genotype
was
associated with an increased risk of larynx cancer among smokers
of 20
g/day or less (OR = 2.9, 95% CI = 1.3-6.3) but not among heavier
smokers (OR = 1.0; 95% CI = 0.5-2.0). In contrast, the GSTT1
null
genotype posed an increased, although not significant, risk among
long-term smokers (OR = 2.3, 95% CI = 0.9-5.4).
Title
Species differences in hepatic pulmonary and upper gastrointestinal
tract biotransformation enzymes on long-term feeding of masheri--a
pyrolyzed tobacco product.
Author
Nair UJ; Ammigan N; Kayal JJ; Bhide SV
Address
Cancer Research Institute' Tata Memorial Centre' Parel' Bombay'
India.
Source
Dig Dis Sci, 36(3):293-8 1991 Mar
Abstract
The activities of several activating enzymes and that of glutathione
S-transferase as well as levels of glutathione were measured
in the
upper alimentary tract' lung' and liver of Swiss mice' Sprague-Dawley
rats' and Syrian golden hamsters treated with 10% masheri (pyrolyzed
tobacco) in diet for 20 months. Significant increase in activities
of
phase I activating enzymes and a remarkable decrease in the phase
II
detoxification system in most extrahepatic tissues of the treated
animals of all three species was observed. These observations
suggest
that the prolonged exposure to environmental xenobiotics/carcinogens
affects the drug-metabolizing enzymes of the gastrointestinal
tract'
which may be an important factor in determining the susceptibility
of
different organs to carcinogen exposure. |
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