26.12.2013 Views

Universlty of Manitoba, ln Partîal Fulfiìlment - MSpace at the ...

Universlty of Manitoba, ln Partîal Fulfiìlment - MSpace at the ...

Universlty of Manitoba, ln Partîal Fulfiìlment - MSpace at the ...

SHOW MORE
SHOW LESS

Create successful ePaper yourself

Turn your PDF publications into a flip-book with our unique Google optimized e-Paper software.

The result <strong>of</strong> any ter<strong>at</strong>ogen¡c insult depends on <strong>the</strong> site <strong>of</strong> action<br />

by <strong>the</strong> agent, and <strong>the</strong> developmenta¡ stage <strong>of</strong> <strong>the</strong> embryo. Thís appl les<br />

to both <strong>the</strong> expression <strong>of</strong> genes, and <strong>the</strong> action <strong>of</strong> environmentâl agents<br />

(saxá, t976).<br />

<strong>ln</strong> general, <strong>the</strong> first period <strong>of</strong> embryonic development (up to <strong>the</strong><br />

form<strong>at</strong>ion <strong>of</strong> germ layers) shows little tendenöy to malfcrm<strong>at</strong>ions, with<br />

embryonic de<strong>at</strong>h <strong>at</strong> high dose levels. lJîth <strong>the</strong> onset <strong>of</strong> morphogenesîs,<br />

<strong>the</strong> embryo become¡ very suscept¡ble to ter<strong>at</strong>ogenlc influences, resultíng<br />

<strong>ln</strong> major malform<strong>at</strong>lons. 0n reaching <strong>the</strong> fetal stêge, only structures<br />

still undergoing differentl<strong>at</strong>lon (such as <strong>the</strong> bra<strong>ln</strong>, pal<strong>at</strong>e, and major<br />

vessels) are stlll susceptlble. to abnormal development (falter, l968).<br />

<strong>ln</strong> mammals, <strong>the</strong>re ls <strong>the</strong> additional problem <strong>of</strong> whe<strong>the</strong>r an êgent<br />

acts directly on <strong>the</strong> embryo or indírectty through <strong>the</strong> placenta, as<br />

exempl ifíed by <strong>the</strong> activity <strong>of</strong> trypan blue. For experimenta¡ ter<strong>at</strong>ology,<br />

<strong>the</strong> use <strong>of</strong> physical agents provîdes accur<strong>at</strong>e control <strong>of</strong> timing and dosage,<br />

though some effects may be secondary to tissue damage or alter<strong>at</strong>ion <strong>of</strong><br />

fiorphogenet i c processes.<br />

X-ray tre<strong>at</strong>ment has revealed <strong>the</strong> sequence <strong>of</strong> crÌtical periods ín<br />

development <strong>of</strong> <strong>the</strong> r<strong>at</strong>(.:lob,et €jL, 19352 Kàven, l!J8; Hicks,.t954), <strong>the</strong> mouse<br />

(Russel l, 1950; 1956; r,rilson, .|954; Hícks, 1954), and <strong>the</strong> chick (Reyss-Brion,<br />

1956; Hadj I tsky,l!62;¡1¡ rrmann and t/olff,1964). Hicks (1954, 1954) found<br />

th<strong>at</strong> irradí<strong>at</strong>ion <strong>of</strong> pregnant r<strong>at</strong>s: <strong>at</strong> 9 days produced an open brain; <strong>at</strong><br />

l0 days produced forebrain, hindbraín, cord, and facial defects; <strong>at</strong> ll<br />

days produced hydrocephalus, with braínstem and cord dèfects; êt l2 days<br />

caused reductÌons <strong>of</strong> <strong>the</strong> brain and eyes; and after thls reduced <strong>the</strong> size<br />

<strong>of</strong> fiber tracts. Hicks found th<strong>at</strong> embryos showed a high regul<strong>at</strong>ive ability<br />

before <strong>the</strong> onset <strong>of</strong> d i ffe ren t i a t i on, so th<strong>at</strong> extensive t¡ssuè damage might<br />

355

Hooray! Your file is uploaded and ready to be published.

Saved successfully!

Ooh no, something went wrong!