536 5. QUINONES 



types of inhibition are different, which is substantiated by the quite dif- 

 ferent cytological sequences observed. Marrian (1959) postulated that X- 

 irradiation interferes with DNA synthesis whereas menadiol-diP inhibits 

 the synthesis of RNA. 



Mitotic Inhibition in Vivo 



Parmentier and Dustin investigated the antimitotic effects of quinones 

 and hydroquinones on the germinal zone of the mouse intestine. Such an 

 effect had first been observed by Zylberszac (1939) following injections 

 of p-benzohydroquinone, and Dustin (1947) had reported extensive nuclear 

 degeneration occurring before the onset of prophase 4 hr after the injection 

 of 125 mg/kg of p-benzohydroquinone. Parmentier and Dustin (1948) 

 believed that a new type of mitotic abnormality is produced. During the 

 first 2 hr there is a progressive accumulation of arrested metaphases, and 

 these generally show small groups of chromosomes migrating toward the 

 poles, although most of the chromosomal material remains at the equatorial 

 plate — these were later termed "three-group metaphases" (Parmentier, 

 1953 a). The central mass is not composed of fragments of broken chromo- 

 somes, nor are they excessively clumped at this stage (although they clump 

 later), nor is there evidence of spindle fiber detachment. They favored the 

 view that division of centromeres is suppressed, especially in the longer 

 chromosomes. Catechol also exerts this action. It was supposed that oxida- 

 tion to the quinone forms occurs and is followed by reaction with SH 

 groups (Parmentier, 1949). The general pycnonecrosis produced is similar 

 to that seen after X-irradiation. Mitotic abnormalities in the ovary, uterus, 

 intestine, and some epithelia are produced in the rabbit by ^^-benzohydro- 

 quinone at doses of 15-175 mg/kg subcutaneously or intraperitoneally 

 (Parmentier, 1953 b). Rats respond similarly, while bone marrow changes 

 can be demonstrated in the hamster (Parmentier, 1953 a). However, Par- 

 mentier's explanation was now different. The chromatic material near 

 the poles was believed to have been left there pre-metaphase, rather than 

 migrating there from the equatorial plate. The question then is: Why does 

 this material not migrate to the equator properly when the bulk of the 

 chromosomes does? In human bone marrow cells, p-benzohydroquinone 

 has a similar effect and the smaller chromosomes do not migrate to the 

 plate; it was observed that the chromatic substance is altered, assuming a 

 fluidlike state until it coagulates into spherical masses. This work was 

 extended by Rosin and Doljanski (1953) to chick fibroblasts, and the liver, 

 cornea, and bone marrow of the rat in vivo. Exposure to p-benzohydro- 

 quinone at 0.009 mM for 1 hr gives typical three-group metaphase cells 

 in fibroblasts and this in vitro effect at least indicates that the action is 

 direct and not through secondary factors. It is rather remarkable that such 

 definite nuclear changes can be induced in animals by nonlethal doses of 



