Monograph on the Potential Human Reproductive and ... - OEHHA
Monograph on the Potential Human Reproductive and ... - OEHHA
Monograph on the Potential Human Reproductive and ... - OEHHA
Create successful ePaper yourself
Turn your PDF publications into a flip-book with our unique Google optimized e-Paper software.
nTp brief<br />
treatment. was. not. significantly. different. from.<br />
c<strong>on</strong>trols.(2/6.versus.1/9.in.c<strong>on</strong>trol.animals)..Proposed.biological.mechanisms.to.account.for.<strong>the</strong>.<br />
effects.of.bisphenol.A.<strong>on</strong>.<strong>the</strong>.prostate.include.an.<br />
epigenetic.mode.of.acti<strong>on</strong>.exemplified.as.altered.<br />
DNA.methylati<strong>on</strong>.patterns.in.genes.that.help.<br />
regulate.prostate.development.<strong>and</strong>.growth.as.an.<br />
epigenetic.mode.of.acti<strong>on</strong>.(51, 194)..PIN.lesi<strong>on</strong>s.<br />
in.<strong>the</strong>.male.rodent.have.similar.histopathology.<br />
to. PIN. lesi<strong>on</strong>s. in. men,. <strong>and</strong>. evidence. of. high.<br />
grade.PIN.lesi<strong>on</strong>s.in.men.is.c<strong>on</strong>sidered.a.risk.<br />
factor.for.developing.prostate.cancer.(96)..The.<br />
use.of.adult.horm<strong>on</strong>e.treatment.to.promote.<strong>the</strong>.<br />
development.of.prostate.intraepi<strong>the</strong>lial.neoplasia.lesi<strong>on</strong>s.complicates.<strong>the</strong>.interpretati<strong>on</strong>.of.this.<br />
study.when.c<strong>on</strong>sidering.its.relevance.to.human.<br />
bisphenol.A.exposure..However,.as.discussed.in.<br />
more.detail.below,.rodents.are.normally.resistent.to.developing.prostate.cancer.<strong>and</strong>.<strong>the</strong>.use.of.<br />
horm<strong>on</strong>e.treatment,.chemical.treatment,.or.o<strong>the</strong>r.<br />
alternative.animal.model.to.obtain.a.more.sensitive.rodent.model.is.c<strong>on</strong>sidered.an.acceptable.<br />
<strong>and</strong>.recommended.strategy.in.prostate.cancer.<br />
research.(187)..<br />
The. findings. of. Ho. et al. (51). are. c<strong>on</strong>sistent.<br />
with.a.recent.report.of.increased.expressi<strong>on</strong>.of.<br />
cytokeratin.10.(CK10),.a.cell-marker.associated.<br />
with. squamous. differentiati<strong>on</strong>,. in. adult. male.<br />
offspring.of.pregnant.mice.orally.treated.with.<br />
0.020.mg/kg.bw/day.bisphenol.A.during.gestati<strong>on</strong>.(195)..Chr<strong>on</strong>ic.exposure.to.high.doses.of.<br />
potent.estrogens,.such.as.diethylstilbestrol,.leads.<br />
to.squamous.metaplasia.of.<strong>the</strong>.prostate,.a.tissue.<br />
change.characterized.by.a.multilayering.of.prostatic.basal.epi<strong>the</strong>lial.cells..Squamous.metaplasia.<br />
is.associated.with.benign.prostatic.hyperplasia.<br />
or. l<strong>on</strong>g-term. estrogen. treatment. in. patients.<br />
with.benign.or.malignant.prostatic.disease..The.<br />
inducti<strong>on</strong>.of.CK10.expressi<strong>on</strong>.in.basal.epi<strong>the</strong>lial.<br />
cells.is.an.early.indicator.of.changes.leading.to.<br />
estrogen-induced.squamous.metaplasia..While.<br />
<strong>the</strong>.l<strong>on</strong>g-term.health.c<strong>on</strong>sequences.of.such.an.<br />
alterati<strong>on</strong>.are.unclear,.prostatic.basal.epi<strong>the</strong>lial.<br />
cells.are.important.for.normal.growth.<strong>and</strong>.devel-<br />
25<br />
opment.<strong>and</strong>.are.implicated.in.<strong>the</strong>.initiati<strong>on</strong>.<strong>and</strong>.<br />
early.progressi<strong>on</strong>.of.prostate.cancer.due.to.<strong>the</strong>ir.<br />
functi<strong>on</strong>.in.maintaining.ductal.integrity.<strong>and</strong>.regulating.<strong>the</strong>.differentiati<strong>on</strong>.of.luminal.epi<strong>the</strong>lial.<br />
cell.differentiati<strong>on</strong>.(192)..It.is.important.to.note.<br />
that.prostates.in.<strong>the</strong>.Ogural.et al..study.appeared.<br />
morphologically. <strong>the</strong>. same. as. c<strong>on</strong>trol. animals.<br />
based.<strong>on</strong>.<strong>the</strong>.staining.technique.normally.used.in.<br />
pathology.(hematoxylin.<strong>and</strong>.eosin,.or.H&E)..A.<br />
stain.specific.for.squamous.keratin.was.required.<br />
to.detect.<strong>the</strong>.change..Thus,.it.is.unclear.whe<strong>the</strong>r.<br />
similar.changes.in.basal.epi<strong>the</strong>lial.cell.phenotype.<br />
were.present.in.o<strong>the</strong>r.studies.that.evaluated.<strong>the</strong>.<br />
prostate.using.<strong>on</strong>ly.an.H&E.stain.<br />
The.NTP.c<strong>on</strong>curs.with.<strong>the</strong>.CERHR.Expert.Panel.<br />
<strong>on</strong>.Bisphenol.A.(2).<strong>and</strong>.ano<strong>the</strong>r.recent.evaluati<strong>on</strong>.(191).that.additi<strong>on</strong>al.studies.are.needed.to.<br />
underst<strong>and</strong>.<strong>the</strong>.effects.of.bisphenol.A.<strong>on</strong>.<strong>the</strong>.<br />
development.of.<strong>the</strong>.prostate.gl<strong>and</strong>.<strong>and</strong>.urinary.<br />
tract..Studies.should.attempt.to.c<strong>on</strong>firm.<strong>the</strong>se.<br />
findings.<strong>and</strong>.include.l<strong>on</strong>ger.periods.of.follow-up.<br />
to.underst<strong>and</strong>.<strong>the</strong>.significance.of.<strong>the</strong>.structural.<br />
<strong>and</strong>.cellular.effects.observed.in.fetuses.<strong>and</strong>.to.<br />
clarify.<strong>the</strong>.relevance.of.prostate.intraepi<strong>the</strong>lial.<br />
neoplastic.lesi<strong>on</strong>s.resulting.from.bisphenol.A.<br />
exposure.to.<strong>the</strong>.development.of.prostate.cancer.in.<strong>the</strong>se.animals..Future.research.to.clarify.<br />
<strong>the</strong>.role.of.bisphenol.A.in.<strong>the</strong>.development.of.<br />
prostate.cancer.presents.a.scientific.challenge..<br />
Unlike.humans.where.prostate.cancer.is.comm<strong>on</strong>,.it.is.<strong>the</strong>.most.comm<strong>on</strong>.n<strong>on</strong>-skin.cancer.<br />
in.American.men.(187),.rodents.rarely.develop.<br />
prostate.cancer..Of.<strong>the</strong>.almost.4,550.rats.<strong>and</strong>.<br />
mice.used.as.c<strong>on</strong>trols.in.NTP.2-year.inhalati<strong>on</strong>.<br />
or.feed.studies.c<strong>on</strong>ducted.during.<strong>the</strong>.last.decade,.<br />
<strong>on</strong>ly.1.cancerous.tumor.<strong>and</strong>.17.benign.tumors.<br />
(“adenoma”).of.<strong>the</strong>.prostate.gl<strong>and</strong>.were.detected.<br />
(187)..No.substances,.including.bisphenol.A.<br />
(176),.have.been.identified.as.causing.prostate.<br />
tumors.in.NTP.studies.(187)..The.NTP.has.l<strong>on</strong>g.<br />
recognized.<strong>the</strong>.limits.of.<strong>the</strong>.traditi<strong>on</strong>al.rodent.<br />
cancer.bioassay.for.detecting.chemical-inducedprostate.tumors.<strong>and</strong>.organized.a.workshop.in.<br />
May.2006.to.address.this.issue.(187)..Suggested.
Change language