Polychlorinated dibenzo-p-dioxins: Quantitative in vitro and in vivo structure-activity relationships

Promotion of Endometriosis in Mice by Polychlorinated Dibenzo-p-Dioxins, Dibenzofurans, and Biphenyls

“…Previous studies showed a correlation between endpoints, such as CYPlAl induction, and affinity for the Ah receptor expressed through SARs (25). For example, in this study 2,3,7,8-TCDD, PCB 126, and 4-PeCDF, the congeners that increased endometriotic lesion diameters (statistically significant only in animals treated with 2,3,7,8-TCDD or 4-PeCDF), have the strongest binding affinities for the Ah receptor (1,26,27). In contrast, compounds such as 1,3,6,8-TCDD and PCB 153, which did not induce any increases in endometriotic lesion diameter, have weak affinities towards the Ah receptor (27,28).…”

“…In this study, constitutive EROD activity in control animals for three separate experiments were similar (Table 1). A statistically 26.7% of the total corpora lutea in control animals, was characterized as regressive. The absence of active corpora lutea and the high percentages of regressive corpora lutea in these dose groups indicate either a direct or indirect chemically induced atrophic effect on the ovaries in these animals.…”

The H4IIE Cell Bioassay as an Indicator of Dioxin-like Chemicals in Wildlife and the Environment

“…The relationship between the induction of CYP1A1 in H4IIE and in vivo toxicity was examined extensively by Safe and coworkers in the 1980s (Bandiera et al, 1984;Safe et al, 1986;Mason et al, 1986). These studies demonstrated that for PCDD and PCDF congeners, comparable structureactivity relationships (SARs) were observed using the H4IIE cell bioassay (AHH and EROD induction), in vitro AhR receptor binding assays, and in vivo responses in immature male Wistar rats (hepatic EROD and AHH activity, thymic atrophy, and body weight loss).…”

“…RPFs for the major classes of CYP1A1 inducers (PHHs) are compiled in Tables 9 and 10. The most complete set of RPFs for PHHs are reported in a series of papers by Safe and coworkers (Sawyer and Safe, 1982;Bandiera et al, 1984;Mason et al, 1986) based on AHH induction. Published RPFs for an individual congener can differ by several-fold depending on the study examined (Tables 9 and 10).…”

Cytochrome P450 1A1 and aromatase (CYP19) in cetaceans : enzyme expression and relationship to contaminant exposure

“…Induction of CYPIA also may be used as a biomarker for effects of the more potent PHAHs, as the toxicity of PHAs, including TCDD, correlates with their ability to induce CYPlA (Poland and Knutson I982;Safe 1986). CYPIA is a member of the cytochrome P450 superfamly of enzymes that catalyze the metabolism of a wide range of both xenobiotics and endogenous compounds in both eukarote and prokarote species (Nelson et al 1996).…”