Metabolism and cytotoxicity of benzo(a)pyrene in the human lung tumour cell line NCI-H322

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Abstract
1. The human lung tumour cells NCI-H322 metabolized benzo(a)pyrene (BP) at a rate of 160 pmol/106 cells/h for at least 8 h. About 30% of the total metabolites were water-soluble, 30% of which were conjugates with glutathione. The water-soluble fraction also contained BP sulphates but no BP glucuronides. 2. The cytotoxic potency of BP and its metabolites, 3-hydroxybenzo(a)pyrene (3-OH-BP) and (±) anti-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene (7,8-diol-BP), differed by an order of magnitude with the ranking 7,8-diol-BP > BP > 3-OH-BP. The cytotoxicity of BP was not detected at the end of a 24 h treatment period but became increasingly apparent at later times. In contrast, the cytotoxicity of 3-OH-BP was observed immediately after the treatment period and did not increase greatly thereafter. 7,8-Diol-BP caused both ‘immediate’ and ‘late’ effects. 3. The time course and concentration dependence suggested that the cytotoxicity of BP in NCI-H322 cells was not attributable to the formation of 3-OH-BP, but more likely resulted from the formation of other products such as 7,8-diol-BP.

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