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

AX5-105
Table AX5-6.18 (cont’d). Genotoxic/Carcinogenic Effects of Lead—Mitogenesis—Animal
Compound Exposure Regimen Species Co-exposure Effects Reference
Pb nitrate Liver initiation induced by the resistant hepatocyte
model (diethylnitrosamine followed by 2acetylaminofluorene
plus carbon tetrachloride) or the
phenobarbital model (diethylnitrosamine plus orotic
acid), or the orotic acid model (diethylnitrosamine
plus orotic acid)
Initiation followed by i.v. injection of Pb nitrate
(100 µM/kg ) or partial hepatectomy, or carbon
tetrachloride by gavage
Animals were studied 6 wks after initiation.
Pb nitrate Liver initiation induced by the resistant hepatocyte
model (diethylnitrosamine followed by
2-acetylaminofluorene plus carbon tetrachloride)
Initiation followed by i.v. injection of Pb nitrate
(100 µM/kg ) or partial hepatectomy, or by gavage:
ethylene dibromide, or cyproterone, or nafenopine
Also tried either 1 or 2 additional i.v. injections of Pb
over 3-day intervals.
Animals were studied at various intervals (1–6 days)
after injection
Pb nitrate Administered as i.v. injection of Pb nitrate
(100 µM/kg ) or partial hepatectomy, or by gavage:
carbon tetrachloride, or ethylene dibromide, or
cyproterone, or nafenopine
Animals were studied at various time intervals
(0.25–24 h) after injection.
Pb nitrate Administered as i.v. injection of Pb nitrate
(100 µM/kg) or partial hepatectomy, or nafenopine by
gavage.
Animals were studied at various time intervals
(24–96 h) after injection.
Pb nitrate Administered as i.v. injection of Pb nitrate
(10 µM/100 g)
Studies for apoptosis at 12, 24, 36, 48, 72, 96, 120,
168, 336 h after injection
Male Wistar
rats—4 per group
Male Wistar
rats—4 per group
Male Wistar
rats—4 per group
Male Wistar
rats—4 per group,
8 wks old
Male Wistar
rats—4 rats per
group
Partial
Hepatectomy,
carbon tetrachloride
Diethylnitrosamine,
2-AAF
Partial
Hepatectomy,
carbon tetrachloride
Pb nitrate, partial hepatectomy, carbon
tetrachloride all stimulated DNA synthesis and
liver cell proliferation
Pb nitrate, did not induce preneoplastic nodules.
Partial hepatectomy and carbon tetrachloride did.
This study aimed to determine if mitogens induce
nodules at different time points.
Pb nitrate, ethylene dibromide, cyproterone, or
nafenopine did not induce preneoplastic nodules
at all. Partial hepatectomy did within 3 days.
Multiple injections of Pb nitrate did not induce
preneoplastic lesions.
Pb nitrate, ethylene dibromide, cyproterone, or
nafenopine induced c-jun and c-myc but did not
induce c-fos.
Partial hepatectomy and carbon tetrachloride
induced c-jun, c-fos, and c-myc.
None Pb nitrate induced a high incidence of polyploidy
and binucleated cells. These changes were
irreversible after 2 wks. Many of these cells were
the newly synthesized cells.
Partial hepatectomy and carbon tetrachloride
induced tetraploid and octaploid mononucleated
cells.
None Liver weight increased until day 5 then returned to
control levels.
DNA synthesis peaked at 36 h
Apoptosis peaked at day 4 and then decreased
gradually.
Ledda-Columbano
et al. (1992)
Coni et al. (1993)
Coni et al. (1993)
Melchiorri et al.
(1993)
Nakajima et al.
(1995)