Our Stolen Futurea book by Theo Colborn, Dianne Dumanoski, and John Peterson Myers
 
 

 

  Go, V, J Garey, MS Wolff and BGT Pogo. 1999. Estrogenic Potential of Certain Pyrethroid Compounds in the MCF-7 Human Breast Carcinoma Cell Line. Environmental Health Perspectives 107:173-177.
 
 

Synthetic pyrethroids are modified versions of a natural chemical, pyrethrin, isolated from chrysanthemums. The modifications make them lipophilic and persistent, increasing the likelihood of accumulation in animal (including human) tissue. Synthetic pyrethroids are used widely as pesticides against "against ticks, mites, mosquitoes (found in bednetting as a control against malaria), and as treatment for human head lice and scabies."

Go et al. test a series of synthetic pyrethroids to determine their ability to disrupt estrogen signalling in experiments using a cell-culture line of human breast cancer cells (MCF-7), using two assays: expression of pS2 and MCF-7 cell proliferation.

The compounds they tested were sumithrin, fenvalerate, d-trans allethrin and permethrin, at concentrations "similar to the amounts necessary to observe the estrogenic properties of various chemicals including o,p-DDT, pesticides, and some polychlorinated biphenyls (PCBs) in various estrogen responsive bioassays."

Each of the compounds caused effects at the levels tested, although the details of the responses varied among the compounds. Higher pyrethrin levels were required to induce effects than for the other three compounds and the effects induced were modest by comparison. In contrast, the other three compounds tested had striking impacts at low levels.

Sumithrin behaved like a classic estrogen mimic. It provoked pS2 induction and cell proliferation at very low levels, but its impact was eliminated when it was combined with an anti-estrogen. This indicates that the mechanism of action of sumithrin is via interaction with the estrogen receptor.

Fenvalerate behaved somewhat differently. It provoked pS2 induction at very low levels, but somewhat higher exposures were required to cause cell proliferation. Its effects on pS2 induction were not eliminated by an anti-androgen. This suggests that at least some of fenvalerate's action may be through a signalling pathway other than the estrogen receptor.

d-trans allethrin (see figure below) at very low levels (1 M) was a moderate estrogen blocker but at higher levels it provoked estrogen-like responses. At even higher levels it was toxic to the cell-line. The resulting dose-response curve had the classic "inverted-U" form of a non-monotonic relationship.

 

pS2 induction by d-trans allethrin (DTA). This graph compares the level of pS2 induction by DTA compared to a positive control (estradiol).

 

The points connected by the dotted line labeled "Inhibition" shows the inhibitory effect of increasing amounts of DTA when it is added to a treatment of estradiol. The higher the concentration, the lower the pS2 induction.

 


Adapted from Go et al. 1999.

The points connected by the solid line labeled "Induction" shows the effect on pS2 induction of DTA by itself. Induction is modest at low levels. It increases in the middle ranges. But at high concentrations induction disappears.

 

 

 

 

 

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