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Phenobarbital and its Sodium Salt - IARC Monographs on the ...

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Table 3 (c<strong>on</strong>td)<br />

Strain (sex) Initiator, dose, route<br />

<str<strong>on</strong>g>and</str<strong>on</strong>g> durati<strong>on</strong><br />

Fischer 344<br />

(M)<br />

Fischer 344<br />

(M)<br />

Fischer 344<br />

(M)<br />

Fischer 344<br />

(M)<br />

NDEA, 150 mg/kg bw,<br />

ip × 2<br />

NDEA, 100 mg/kg bw,<br />

ip × 1/week, 3 weeks<br />

NDEA, 200 mg/kg bw,<br />

ip; 2 weeks later, Dgalactosamine,<br />

300<br />

mg/kg bw, ip at <strong>the</strong><br />

end of weeks 2 <str<strong>on</strong>g>and</str<strong>on</strong>g> 5<br />

NDEA, 200 mg/kg ip,<br />

PH at week 3<br />

Interval<br />

between<br />

initiator <str<strong>on</strong>g>and</str<strong>on</strong>g><br />

promoter<br />

Dose <str<strong>on</strong>g>and</str<strong>on</strong>g> durati<strong>on</strong> of PB or<br />

NaPB <str<strong>on</strong>g>and</str<strong>on</strong>g> route<br />

4 m<strong>on</strong>ths PB, 10, 100 or 500 mg/kg<br />

diet for 7, 30 or 60 days<br />

1 week PB, 500 mg/kg diet, 20<br />

weeks or PB + 100 mg/kg<br />

diet MMTS, 20 weeks<br />

2 weeks PB, 500 mg/kg diet, weeks<br />

3–8<br />

2 weeks PB, 1, 2, 4, 7.5, 15 or 500<br />

mg/kg diet, 6 weeks<br />

PB, 0.01, 0.1 or 0.5 mg/kg<br />

diet, 6 weeks<br />

PB, 1, 2, 4, 7.5, 15, 30, 60,<br />

125, 250 or 500 mg/kg diet,<br />

6 weeks<br />

Promoting or anti-promoting effects<br />

<strong>on</strong> preneoplastic or neoplastic<br />

hepatocellular lesi<strong>on</strong>s<br />

Eosinophilic foci; growth at 100 (7<br />

<str<strong>on</strong>g>and</str<strong>on</strong>g> 60 days), 500 (30 <str<strong>on</strong>g>and</str<strong>on</strong>g> 60 days)<br />

mg/kg diet; at 10 mg/kg diet, PB was<br />

ineffective<br />

GST-P-positive foci; promoti<strong>on</strong> with<br />

PB; inhibiti<strong>on</strong> with PB + MMTS<br />

GST-P-positive foci; promoti<strong>on</strong> by<br />

PB; multiple injecti<strong>on</strong> of D-galactosamine<br />

as effective as PH<br />

GST-P- <str<strong>on</strong>g>and</str<strong>on</strong>g> TGF-α-positive foci;<br />

promoti<strong>on</strong> at 500 mg/kg diet;<br />

inhibiti<strong>on</strong> at 1, 2, 4, 7.5 mg/kg diet<br />

No promoti<strong>on</strong><br />

GST-positive foci; promoti<strong>on</strong> at<br />

doses higher than 15 mg/kg diet;<br />

inhibiti<strong>on</strong> at 2 <str<strong>on</strong>g>and</str<strong>on</strong>g> 4 mg/kg diet<br />

Reference<br />

Kolaja et al.<br />

(1996b)<br />

Sugie et al.<br />

(1997)<br />

Kim et al.<br />

(1997)<br />

Kitano et al.<br />

(1998)<br />

194<br />

<str<strong>on</strong>g>IARC</str<strong>on</strong>g> MONOGRAPHS VOLUME 79

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