Aryl hydrocarbon hydroxylase inducibility among primary relatives of children with leukemia or solid tumors.
In mice, there is a correlation between genetically regulated levels of inducible aryl hydrocarbon hydroxylase (AHH) activity and the risk of polycyclic hydrocarbon-induced leukemia or solid tumors. Recent clinical studies suggest a relationship between high AHH activity and lung cancer associated with cigarette smoking (Kouri, R.E., McKinney, C.E., Slomiany, D.J., Snodgrass, D.R., Wray, N.P., and McLemore, T.L. Cancer Res. 42: 5030-5037, 1982). To determine whether there is a similar genetic relationship in humans between inducible AHH and the occurrence of pediatric cancers, we examined AHH activity in mitogen-stimulated benzo(a)anthracene-treated lymphocyte cultures from primary relatives of children with leukemia or solid tumors. Control families (parents and siblings with no history of cancer) comprised friends or neighbors of the proband families. By comparing variance among family members with variance among nonrelated individuals, we conclude that a small, but real, genetic component is detectable. Adjusting for age, smoking history, and the length of time during which the lymphocytes had been cryopreserved, however, we find no difference among 77 leukemia, 71 solid tumor, and 100 control family members with regard to median units (+/- median S.E.) of maximally induced AHH activity per unit of reduced nicotinamide adenine dinucleotide-cytochrome c reductase activity: 0.31 +/- 0.03; 0.28 +/- 0.03; and 0.28 +/- 0.03, respectively. Thus, benzo(a)anthracene-induced AHH activity in cultured mitogen-activated lymphocytes in our study population does not appear to be associated with the risk of occurrence of childhood leukemia or solid tumors.
D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D002478:Cells, Cultured; D002648:Child; D004261:DNA Replication; D004790:Enzyme Induction; D006801:Humans; D007938:Leukemia / Q000201:enzymology / Q000235:genetics*; D008214:Lymphocytes / Q000201:enzymology* / Q000378:metabolism; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics*
D001189:Aryl Hydrocarbon Hydroxylases