Alterations in cytochrome P-450 levels in adult rats following neonatal exposure to xenobiotics

Journal Article · Fri Jan 01 00:00:00 EST 1993 · Journal of Toxicology and Environmental Health; (United States)

DOI:https://doi.org/10.1080/15287399309531699· OSTI ID:6697999

Zangar, R C ^[1]; Springer, D L ^[2]; Buhler, D R ^[3]

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1. Oregon State Univ., Corvallis (United States) Pacific Northwest Laboratories, Richland, WA (United States)
2. Pacific Northwest Laboratories, Richland, WA (United States)
3. Oregon State Univ., Corvallis (United States)

Neonatal exposure to certain xenobiotics has been shown to alter hepatic metabolism in adult rats in a manner that indicates long-term changes in enzyme regulation. Previously, the authors have observed changes in adult testosterone metabolism and in cytochrome P-450 (P-450) mRNA levels in animals neonatally exposed to phenobarbital (PB) or diethylstilbestrol (DES). In order to test for other enzyme alterations, they used Western blot procedures for specific P-450s to analyze hepatic microsomes from adult rats (24 wk old) that had been exposed neonatally to DES, PB, 7,12-dimethylbenz[a]anthracene (DMBA), or pregnenolone 16[alpha]-carbonitrile (PCN). The most striking effects were observed in the DES-treated males: P-4502C6 and an immunologically similar protein were increased 60 and 90%, respectively, relative to control values, but P-4503A2 was decreased by 44%. No changes were observed in the DES-treated males in levels of P-4502E1, P-4502B, or the male-specific P-4502C13. Adult males neonatally treated with PB had 150% increase in levels of anti-P4502B-reactive protein without significant changes in the other enzymes. The DES- and DMBA-treated females had increased levels of the female-specific P-4502C12 of 38 and 48%, respectively, but no other observed alterations. The results confirm that neonatal exposure to DES or PB can cause alterations in adult hepatic cytochrome P-450 levels but show that these chemicals act on different enzymes. Neonatal DMBA resulted in changes in adult females similar to those produced by the synthetic estrogen DES, but did so at about two-thirds lower dose. 37 refs., 5 figs.

• DOE Contract Number: AC06-76RL01830; FG06-89ER75522
• OSTI ID: 6697999
• Journal Information: Journal of Toxicology and Environmental Health; (United States), Vol. 38:1; ISSN 0098-4108
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANTHRACENE
PRENATAL EXPOSURE
ENZYMES
ULTRASTRUCTURAL CHANGES
PHENOBARBITAL
RATS
LIVER
XENOBIOTICS
ANIMALS
CYTOCHROMES
FEMALES
MALES
METABOLISM
MICROSOMES
PROTEINS
TESTOSTERONE
ANDROGENS
ANDROSTANES
ANESTHETICS
ANTICONVULSANTS
AROMATICS
AZINES
BARBITURATES
BODY
CELL CONSTITUENTS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
CONDENSED AROMATICS
DIGESTIVE SYSTEM
DRUGS
GLANDS
HETEROCYCLIC COMPOUNDS
HORMONES
HYDROCARBONS
HYDROXY COMPOUNDS
HYPNOTICS AND SEDATIVES
KETONES
MAMMALS
MORPHOLOGICAL CHANGES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANS
PIGMENTS
PYRIMIDINES
RIBOSOMES
RODENTS
STEROID HORMONES
STEROIDS
VERTEBRATES
550200* - Biochemistry
560300 - Chemicals Metabolism & Toxicology