A case of common variable hypogammaglobulinaemia with associated impairment of cell mediated immunity and severe wart virus infection is described. The defect of cell mediated immunity is thought to have predisposed this patient to the development of persistent wart infection which in turn grossly depressed the body's cellular immunity and thus allowed widespread dissemination of the warts. The rapid restoration of cell mediated immunity which followed the reduction in the antigenic load of wart virus by diathermy treatment was followed by the spontaneous regression of all the patient's warts. This unusual case may provide some insight into the complex relationship between wart virus infection and the immune system of the host.

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7,12-DIMETHYLBENz(a)ANTHRACENE (DMBA) given in a single dose (30 mg.). in oil by stomach tube or intravenously (5 mg.) in lipid emulsion induces mammary tumours in Sprague-Dawley rats within 2-3 months (Huggins, Briziarelli and Sutton, 1959;Huggins, Grand and Brillantes, 1961), and also causes severe adrenal necrosis within 2-3 days (Huggins and Morii, 1961). We have shown that DMBA itself is probably not responsible for adrenal necrosis (Wheatley, Kernohan and Currie, 1966;Wheatley, Hamilton, Currie, Boyland and Sims, 1966) but must first be metabolized by the liver. Boyland and Sims (1965) found that DMBA is metabolized by rat liver mainly by hydroxylation of the methyl groups; 7-hydroxymethyl-12-methylbenz(a)anthracene is probably the adrenocorticolytic metabolite (Boyland, Sims and Huggins, 1965;Wheatley, Hamilton, Currie, Boyland and Sims, 1966). Boyland et al. (1965) tested the carcinogenicity of DMBA and its hydroxymethyl derivatives in rats and mice. Briefly, the 7-hydroxymethyl derivative induced mammary tumours but with a longer mean induction time than DMBA whereas the 12-hydroxymethyl derivative was not carcinogenic in rats although it was in mice.It is also possible that a metabolite of DMBA, and not DMBA itself, is responsible for tumour induction. We have therefore tested the ability of DMBA ta produce tumours in rats with impaired liver function. MATERIALS AND METHODSSprague-Dawley female rats from an accredited stock were obtained from Oxford Laboratory Animal Colonies, Oxford, England. CC14 (AnalaR) was given to 60 rats at a dose of 0 3 ml. of a 50% solution in olive oil intraperitoneally.Forty-three rats were partially hepatectomized, two-thirds of the liver being removed by the method of Higgins and Anderson (1931). Forty rats were given olive oil intraperitoneally (013 ml.) as controls. Twenty-four hours later the rats received 5 mg. DMBA in 1V0 ml. 15 % cottonseed oil emulsion via a lateral tail vein. At the time of DMBA injection rats were 50 days old and weighed about 150 g.The severity of the combined treatments resulted in a high early mortality. The surviving rats were palpated twice a week from the fourth week after injection. Tumours were measured and charted as described previously (Stevens, Stevens and Currie, 1965). The experiment was terminated at 6 months and an assessment

Summary.-Further investigations into the mechanism by which CC14 administration to Sprague-Dawley rats protects them against the adrenocorticolytic action of dimethylbenz(a)anthracene (DMBA) are reported. The results show that CC14 must be given shortly before DMBA to achieve the best protection and that treatments given after DMBA are ineffective. It was established that the hepatotoxicity of CCI4 in these experiments was related reciprocally to the adrenocorticolytic effect of DMBA.Protection with butter yellow (DAB) was achieved only when sufficient time elapses for drug metabolism to be stimulated in the liver. Butter yellow given after DMBA has no protective effect but the prior exposure of the rats to DMBA potentiates the hepatotoxic effects of DAB.Partial hepatectomy gives protection when performed 1 day before DMBA; shorter intervals give no protection. Some protection can be achieved with resection 6 or 24 hours after DMBA.NECROSIS of the adrenal cortex of the mature Sprague-Dawley rat induced by 7,12-dimethylbenz(a)anthracene (DMBA) can be prevented by treatment with carbon tetrachloride or by partial hepatectomy 24 hours before administration of the polycyclic compound (Wheatley, Kernohan and Currie, 1966b). This finding was the first indication that DMBA can only exert an adrenocorticolytic effect after it has been metabolized by the liver, Subsequent work has proved this to be the case and has shown that 7 -hydroxymethyl-12 -methylbenz (a) -anthracene is either an intermediate or a superior substrate from which the ultimate adrenal damaging agent arises (Boyland, Sims and Huggins, 1965;Wheatley et al., 1966a;Wheatley and Sims, 1969).The time intervals between treatments designed to impair liver function and the administration of DMBA are critical for achieving protection of the adrenal gland. In our original communication (Wheatley et al., 1966b) we confined our results to an interval of one day at which time the hepatotoxic action of CC14 was most pronounced and the effect of partial hepatectomy in altering liver function towards regeneration was maximal. The effects of varying the interval have proved to be very informative, however, and in this report the results with three methods of interfering with liver function -(i) CC14 treatment, (ii) p-dimethylaminoazobenzene (butter yellow, hereafter DAB), and (iii) partial hepatectomy (700o) are described. An interesting reciprocal relationship is shown between the protective action of pretreatments with hepatotoxins on adrenocorticolysis by DMBA, and effects of pretreatment with DMBA on the action of the hepatotoxins. It is also shown that normal liver functioning at the time of DMBA administration is indeed critical for the production of adrenocorticolysis and that the induction of liver damage with hepatotoxins after DMBA administration has little or no effect on the adrenocorticolytic phenomenon.