Reply

I. Glenn Sipes1, Patricia B. Hoyer2 and P. J. Devine2

Department of Pharmacology and Toxicology The University of Arizona Tucson, AZ 85724 2 Department of Physiology The University of Arizona Tucson, AZ 85724

To the Editor:

We appreciate the letter by Huff which informs readers of Toxicological Sciences of the NTP bioassays that evaluated the carcinogenicity of 4-vinylcyclohexene(4-VCH) and 4-vinylcyclohexene diepoxide (4-VCHD). Indeed, it was the results of these studies that sparked our interest in 4-VCH and 4-VCHD. The susceptibility of the female mouse to ovarian lesions/carcinogenicity caused by 4-VCH (and the resistance of the rat) provided a model that has advanced the knowledge base on chemical-induced follicular loss. This model has established that bioactivation of 4-VCH to 4-VCHD (a two step process) is required for follicular loss. It also demonstrated that the mouse is susceptible to ovarian lesions because, when compared to the rat, it forms more 4-VCHD. This is coupled with a reduced capacity to detoxify 4-VCHD via epoxide hydrolase. Importantly, 4-VCHD has been used to elucidate the molecular mechanism(s) by which ovarian follicles are destroyed. 4-VCHD follicular loss is caused by apoptosis which appears to result from an acceleration of the frequency or occurrence of atresia. Clearly, our studies and those of many others were initiated as a result of the NTP bioassays referred to in the letter by Huff.





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