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The effect of chemotherapy on natural killer (NK) activity and antibody-dependent cell-mediated cytotoxicity (ADCC) in 15 advanced carcinomas of the lung was examined with regard to the drug, dose, route and timing of administration. The relationship between the effect of chemotherapy on the prognosis for the patients, and the changes in NK activity and ADCC, was also analysed. The NK activity and ADCC in patients with poor prognosis were significantly subnormal, even before treatment. The NK activity and ADCC began to decrease 2 weeks after the initiation of treatment and reached the lowest level during the 3rd or 4th week in all patients. Thereafter, they returned to the pretreatment level in 8 patients with stabilized disease. In contrast, they were not restored in 7 patients with progressive disease and poor prognosis. In 4 patients it was found that the effect of chemotherapy with pepleomycin and carbazilquinone on NK activity and ADCC differed according to the drug used. From this pilot study it is suggested that NK activity and ADCC are valuable prognostic factors in patients with advanced carcinoma of the lung, and that detailed analysis of the effect of each anticancer agent on NK activity and ADCC is desirable for the establishment of better treatment regimens for advanced carcinoma of the lung.

Tight linkage between the hemochromatosis locus and the HLA region permits determination of genotype in members of hemochromatosis pedigrees. To determine if simple laboratory measures of iron metabolism could predict the affected genotype without the need for HLA typing, we studied seven measures of iron metabolism: serum iron concentration, total iron-binding capacity, per cent saturation of transferrin, serum ferritin concentration, deferoxamine-induced urinary iron excretion and hepatic iron concentration evaluated by both chemical and histological methods. Discriminant analysis showed a per cent saturation of transferrin above 62% to be the best simply-measured indicator of the affected genotype: homozygosity is accurately predicted in 92% of the cases. The logarithmic transform of serum ferritin concentration was only 71% accurate. Pedigree analysis estimated the frequency of the hemochromatosis gene at 0.069 +/- 0.020 with a recombination probability of 0.015 +/- 0.015 with the HLA region. This corresponds to a heterozygote frequency of 0.13 and a disease frequency of 0.005.

In vivo treatment with antineoplastic compounds has been reported to lead to the expression of new antigenic specificities which were not detected on parental cells, and which were transmissible as a genetic character. The current study is concerned with antibody-dependent cellular cytotoxic (ADCC) activity in serum of syngeneic mice challenged with LY/DTIC cells, a subline of LY murine lymphoma, antigenically altered by the drug DTIC. LY/DTIC target cells coated with LY/DTIC-immune serum were specifically lysed by virgin lymphocytes. The genetic background of the effector cells, whether syngeneic, allogeneic or xenogeneic, did not produce significant differences in the percentage of target-cell lysis. ADCC activity was reduced when the immune serum was added directly to the incubation medium, without precoating. Although sera from individual animals exhibited different levels of ADCC activity, they nevertheless followed the general trend of the pooled sera. Peak activity of ADCC was obtained in the sera collected on Days 8 and 30 after LY/DTIC cell challenge. The ADCC activity elicited by LY/DTIC cells may contribute to the rejection of drug-altered tumour cells.