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Air Quality Criteria for Lead Volume II of II - (NEPIS)(EPA) - US ...

Air Quality Criteria for Lead Volume II of II - (NEPIS)(EPA) - US ...

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AX5-13<br />

Table AX5-2.6. <strong>Lead</strong>, Heme, and Cytochrome P–450<br />

Dose and Route <strong>of</strong><br />

exposure Duration Species Blood lead Effect Authors<br />

0–75 mg <strong>of</strong> Pb 2+ /Kg b.<br />

wt. i.p., Single<br />

injection<br />

EROD—Ethoxy resorufin-O-dealkylase.<br />

CYp3a11—Cytochrome P-450 3a11.<br />

0–30 h C57 BL/6 male mice — Pb causes an increase in *-amino levulinic acid levels in plasma and a<br />

decrease in the heme saturation <strong>of</strong> hepatic tryptophan -2,3 dioxygenase.<br />

P-450- dependent activities, EROD and O-dealkylation <strong>of</strong><br />

alkoxyresorufins decreased progressively. Pb exposure decreased<br />

mRNA levels <strong>of</strong> the P450 CYp3a11. The decrease in P450 transcription<br />

was a mechanism dependent on heme by inhibition <strong>of</strong> heme synthesis<br />

and also by a mechanism independent <strong>of</strong> heme in which Pb decreases P-<br />

450 transcription.<br />

Jover et al. (1996)

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