RESUMO
Dentists can be effective in helping their patients achieve smoking cessation. To plan a didactic program, we explored the smoking cessation attitudes and practices of dental students and identified barriers to service provision in the dental setting. We assessed 244 fourth-year dental students at New York University College of Dentistry through a self-report survey. The instrument included a twenty-nine-item measure assessing attitudes towards tobacco-use counseling and adherence to National Cancer Institute tobacco cessation guidelines. The survey also assessed demographics, tobacco use history, and level of preparation to provide services. Generally, students endorsed tobacco prevention practices, but perceived barriers to service provision. Students provided counseling inconsistently, with 69 percent asking about smoking, 58 percent advising cessation, 24 percent offering assistance, and 22 percent providing followup on a routine basis. Those who provided more counseling were more likely to have undergone formal training in smoking cessation, did not feel time was a barrier to counseling, and had more favorable beliefs about dentists' role in promoting smoking cessation. Study findings indicate great receptivity among students as well as a critical need and opportunity to include comprehensive cessation counseling training in the dental curriculum.
Assuntos
Atitude do Pessoal de Saúde , Guias de Prática Clínica como Assunto , Abandono do Hábito de Fumar/psicologia , Estudantes de Odontologia/psicologia , Adulto , Barreiras de Comunicação , Demografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque , Abandono do Hábito de Fumar/métodos , Estatísticas não Paramétricas , Estudantes de Odontologia/estatística & dados numéricos , Inquéritos e QuestionáriosRESUMO
When water traps baited with allyl isothiocyanate (AIC)diffusing through polyvinyl chloride (PVC) and rubber membranes were used to monitor four species of crucifer-feeding flea beetle adults in a rutabaga field at L'Assomption, Que. in 1980-1981, differential responses to AIC were observed.Phyllotreta cruciferae was more attracted to AIC thanP. striolata, whereas the behavior ofPsylliodes punctulata was not affected by the presence of AIC. The traps with the PVC membrane caught significantly more flea beetles than the traps with the rubber membrane in 1980, but caught a similar number in 1981. Sticky traps covered with AIC mixed with Tangletrap® caught significantly more flea beetles than control sticky traps.
RESUMO
The parasitoid Anagyrus kamali Moursi was recently introduced into the Caribbean as a biological control agent against the hibiscus mealybug, Maconellicoccus hirsutus Green. In the laboratory, parasitoid size, as measured by left hind tibia length, was positively correlated with several indicators of the parasitoid's fitness: longevity, mating preference, fecundity, reproductive longevity, progeny emergence and sex-ratio. When fed ad libidum with honey drops, large male parasitoids lived significantly longer (29.1 +/- 6.5 days) than small ones (18.4 +/- 5.7 days). Large females also lived significantly longer (35.4 +/- 10 days) than small females (27.9 +/- 9.6 days). Females showed no significant mating preference between large and small males. Lifetime fecundity was positively correlated with the size of adult females and ranged from 37 +/- 21 eggs for small females to 96 +/- 43 eggs for large ones. The reproductive longevity, daily oviposition rate, and number of progeny were also higher among large parasitoids. The sex ratio of progeny from small female parasitoids was higher (0.76 +/- 0.24) than that of large individuals (0.47 +/- 0.18).
Assuntos
Vespas/fisiologia , Animais , Constituição Corporal , Feminino , Fertilidade , Longevidade , Masculino , Razão de Masculinidade , Comportamento Sexual AnimalRESUMO
Aflatoxin B1 (AFB1) is a potent hepatotoxic and hepatocarcinogenic mycotoxin that requires bioactivation to AFB1-2,3-oxide for activity. In addition to epoxidation, microsomal monooxygenases biotransform AFB1 to the less toxic metabolites, aflatoxin M1 (AFM1) and aflatoxin Q1 (AFQ1). The lung is at risk from AFB1 both via inhalation and via the circulation. In the present study, we have characterized rabbit lung and liver microsomal AFB1-DNA binding (an index of AFB1-2,3-oxide formation), AFM1 formation and AFQ1 formation. Vmax values for AFB1-DNA binding were not different between lung and liver when expressed per mg microsomal protein (1.06 +/- 0.13 and 2.12 +/- 1.30 nmol/mg/h for lung and liver respectively), but lung values were greater than liver when expressed per nmol cytochrome P450 (3.64 +/- 0.31 and 1.29 +/- 0.70 nmol/nmol P450/h for lung and liver respectively). Km values for this reaction were not different between lung and liver. Vmax values for AFM1 formation in liver microsomes were greater than in lung when expressed per mg protein, but not when expressed per nmol P450. No differences were detected for the Km for AFM1 formation between lung and liver microsomes. For AFQ1 formation, no differences were detected between Vmax values of lung and liver, regardless of whether results were expressed per mg protein or per nmol P450, while the Km for AFQ1 formation was lower in liver. SKF-525A inhibited these reactions by 63-74% in lung microsomes and 90-96% in liver microsomes. These results indicate that the lung is capable of activating AFB1, and that rabbit lung microsomes contain high activity for this reaction. Furthermore, little AFM1 and AFQ1 are formed in lung microsomes, leading to minimal shunting of AFB1 from the activation pathway.
Assuntos
Aflatoxinas/farmacocinética , Carcinógenos/farmacocinética , Microssomos Hepáticos/metabolismo , Microssomos/metabolismo , Aflatoxina B1 , Aflatoxina M1 , Aflatoxinas/biossíntese , Animais , Biotransformação , DNA/metabolismo , Cinética , Pulmão/metabolismo , Pulmão/ultraestrutura , Masculino , NADP/metabolismo , Piridinas/farmacologia , CoelhosRESUMO
In order to study the mechanism of cancer production by aflatoxin B1 (AFB1) in extrahepatic tissues which have relatively low cytochrome P450 monooxygenase (P450) activity, we have examined prostaglandin H synthase (PHS)-mediated AFB1 activation [( 3H]AFB1-DNA binding). [3H]AFB1 was activated by both purified PHS and microsomal PHS from guinea-pig kidney and liver, as well as by P450 in lung, kidney and liver microsomes, though P450-mediated [3H]AFB1-DNA binding in lung and liver was much higher than that catalyzed by PHS. Arachidonic acid (AA)-dependent [3H]AFB1-DNA binding could be inhibited by the PHS inhibitor indomethacin (0.1 mM), but was enhanced by the P450 inhibitor SKF-525A (3 mM), confirming that the reaction was independent of P450. Pulmonary PHS-mediated [3H]AFB1--DNA binding was less than 0.1 pmol [3H]AFB1/mg protein/min. HPLC analysis showed only minimal formation of [3H]AFM1 and [3H]AFQ1 by PHS, confirming that the low rate of PHS-dependent [3H]AFB1-DNA adduct formation was not due to conversion of AFB1 to other metabolites by PHS. The omission of AA did not diminish [3H]AFB1-DNA binding. In AA-free incubates, indomethacin inhibited, and SKF-525A enhanced, [3H]AFB1-DNA binding to a similar degree as in complete incubates, indicating that DNA binding in AA-free incubates was catalyzed by PHS. This reaction was also inhibited by 4-bromophenacyl bromide, a phospholipase A2 inhibitor, by 92%. These data are consistent with previous reports indicating the ability of AFB1 to stimulate the release of endogenous AA from membranes, presumably by stimulating phospholipase A2 activity, which may lead to enhanced bioactivation of AFB1 by PHS in vivo.
Assuntos
Aflatoxinas/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , DNA/metabolismo , Rim/metabolismo , Pulmão/metabolismo , Microssomos/metabolismo , Oxigenases/metabolismo , Prostaglandina-Endoperóxido Sintases/metabolismo , Aflatoxina B1 , Animais , Cobaias , Microssomos Hepáticos/metabolismoRESUMO
The cytotoxic and carcinogenic mycotoxin aflatoxin (AF) B1 (AFB1) is biotransformed by the cytochrome P450 monooxygenases (CYP) to a number of relatively nontoxic metabolites, as well as to the ultimate toxic metabolite, AFB1-8,9-epoxide. In a number of tissues and species, AFB1 hydroxylation to the relatively nontoxic metabolite, AFM1, is induced by beta-naphthoflavone (BNF) treatment. Although the liver is the principle target organ for AFB1 toxicity, the mycotoxin is also toxic and carcinogenic to respiratory tissues. To determine if BNF treatment alters the extent of pulmonary AFB1 bioactivation by enhancing detoxification and thereby decreasing epoxidation, the effects of BNF on pulmonary AFB1 metabolism were examined. Rabbit lung cells, isolated by protease digestion and centrifugal elutriation, were incubated with [3H]AFB1. In nonciliated bronchiolar epithelial (Clara) cell-enriched (45-50%) fractions, [3H]AFM1 production (pmol/mg DNA per 2 h) was increased by prior treatment of rabbits with BNF (80 mg/kg per day, 3 and 2 days before cell isolation) as follows: with 1.0 microM [3H]AFB1; control, 10.6 +/- 2.3; BNF, 30.0 +/- 6.4; with 0.10 microM [3H]AFB1; control, 9.4 +/- 4.7; BNF, 20.6 +/- 5.9. With 1.0 microM [3H]AFB1, prior treatment of animals with BNF abolished formation of [3H]aflatoxicol (AFL) but not [3H]AFQ1. The activation (epoxidation) of [3H]AFB1 was measured indirectly as covalent binding to endogenous DNA. With 1.0 microM [3H]AFB1, treatment of rabbits with BNF did not alter DNA binding (pmol/mg DNA per 2 h) in the Clara cell-enriched fraction: control, 103 +/- 41; BNF, 114 +/- 49. However, with 0.10 microM [3H]AFB1, DNA binding in the same fraction was 47% lower in cells from BNF treated animals: control, 17.4 +/- 4.2; BNF, 9.3 +/- 3.9. Formation of 8,9-dihydro-8,9-dihydroxy-AFB1, and the glutathione conjugate of the aflatoxin epoxide (AFB1-GSH) were not detectable at the AFB1 concentration and time point studied, in cells from either BNF-treated or control rabbits. Incubation of isolated, unseparated lung cells from untreated rabbits with 5.0 to 50 microM BNF decreased [3H]AFB1-DNA binding in the presence of 0.1 microM [3H]AFB1 by 35 to 77%, while lower BNF concentrations did not alter DNA binding. In lung cells isolated from BNF treated rabbits, BNF was not detectable (i.e. < 0.5 microM detection limit). Therefore, the amount of BNF present in isolated rabbit lung cells following in vivo treatment with BNF was below that required to directly inhibit AFB1-DNA adduct formation. The decrease in AFB1-DNA binding from rabbits treated with BNF is apparently due to the selective induction of CYP isozymes and related increases in AFM1 formation, and not to direct inhibition of epoxidation or enhanced conjugation of AFB1-8,9-epoxide with glutathione.
Assuntos
Aflatoxina B1/metabolismo , Pulmão/efeitos dos fármacos , Mutagênicos/metabolismo , beta-Naftoflavona/farmacologia , Animais , Biotransformação/efeitos dos fármacos , Células Cultivadas , DNA/metabolismo , Pulmão/metabolismo , Masculino , CoelhosRESUMO
Aflatoxin B1 (AFB1) requires bioactivation to AFB1-8,9-epoxide for carcinogenicity, and glutathione S-transferase (GST)-catalyzed conjugation of activated AFB1 with glutathione (GSH) is a critical determinant of susceptibility to the mycotoxin. Incubations containing [3H]AFB1, rabbit liver microsomes, an NADPH-generating system, 1 mM GSH, and GST-containing lung or liver cytosol were performed to assess the abilities of lung and liver GSTs to conjugate AFB1-8,9-epoxide. [3H]AFB1-GSH was isolated by isocratic reverse-phase high-performance liquid chromatography (HPLC) and quantitated by liquid scintillation spectroscopy. Maximal [3H]AFB1-GSH formation rates were significantly lower for lung than for liver (0.3 +/- 0.1 and 1.7 +/- 0.4 nmol/mg/hr, respectively). Immunoprecipitation of rabbit pulmonary cytosolic GSTs with anti-alpha or anti-mu GST antisera decreased [3H]AFB1-GSH production by approximately 45 and 51%, respectively, indicating that alpha-class and mu-class GSTs are of similar importance in catalyzing this reaction in the lung. Because mu-class GSTs comprise only a small proportion of total lung GST content, these enzymes have high specific activity toward AFB1-8,9-epoxide. In contrast, the pi-class GST appeared to play a negligible role. Using a rat liver microsomal system to generate both AFB1 exo- and endoepoxide isomers, and analysis based on chiral HPLC, we found that rabbit liver cytosolic GSTs catalyzed formation of both AFB1 exo- and endo-epoxide-GSH conjugates, whereas pulmonary cytosolic GSTs catalyzed formation of only the exo stereoisomer at detectable levels. Despite a preference for conjugating the more mutagenic AFB1 exo-epoxide isomer, the relatively low capacity for GST-catalyzed detoxification of bioactivated AFB1 in lung may be an important factor in the susceptibility of the lung to AFB1 toxicity.
Assuntos
Aflatoxina B1/metabolismo , Aflatoxina B1/farmacocinética , Glutationa Transferase/metabolismo , Glutationa Transferase/fisiologia , Fígado/enzimologia , Fígado/metabolismo , Pulmão/enzimologia , Pulmão/metabolismo , Animais , Biotransformação/efeitos dos fármacos , Catálise , Cromatografia Líquida de Alta Pressão , Compostos de Epóxi/metabolismo , Immunoblotting , Fígado/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Masculino , Testes de Precipitina , Coelhos , RatosRESUMO
Aflatoxin B1 (AFB1) is a fungal toxin that has been implicated as a causative agent in human hepatic and extrahepatic carcinogenesis. In this review, the mechanisms involved in AFB1 toxicity are delineated, in order to describe the features that make a specific cell, tissue, or species susceptible to the mycotoxin. Important considerations include: (i) different mechanisms for bioactivation of AFB1 to its ultimate carcinogenic epoxide metabolite; (ii) the balance between bioactivation to and detoxification of the epoxide; (iii) the interaction of AFB1 epoxide with DNA and the mutational events leading to neoplastic transformation; (iv) the role of cytotoxicity in AFB1 carcinogenesis; (v) the significance of nonepoxide metabolites in toxicity; and (vi) the contribution of mycotoxin-unrelated disease processes. Although considerable controversy remains about the importance of specific events, a great deal has been learned about biochemical and molecular actions of AFB1.
Assuntos
Aflatoxina B1/toxicidade , Neoplasias/induzido quimicamente , Aflatoxina B1/metabolismo , Animais , Biotransformação , Sistema Enzimático do Citocromo P-450/fisiologia , Epóxido Hidrolases/fisiologia , Compostos de Epóxi/metabolismo , Genes p53/efeitos dos fármacos , Glutationa Transferase/fisiologia , Humanos , Pulmão/metabolismo , Proto-Oncogenes/efeitos dos fármacosRESUMO
Glutathione-S-transferase-catalyzed conjugation of glutathione (GSH) to aflatoxin B1-8,9-epoxide plays an important role in preventing binding of this ultimate carcinogen to target macromolecules. Once formed, the aflatoxin B1-epoxide-GSH conjugates are actively extruded from the cell by an unidentified ATP-dependent export pump or pumps. Two possible candidates for this GSH conjugate pump are the 190-kDa multidrug resistance protein (MRP) and the 170-kDa P-glycoprotein. Both proteins belong to the ATP-binding cassette superfamily of transmembrane transport proteins and confer resistance to a similar spectrum of natural-product drugs. Using membrane vesicles from MRP-transfected cells, we found that MRP transports GSH conjugates of both the endo-isomers and exo-isomers of aflatoxin B1-8,9-epoxide in an ATP-dependent, osmotically sensitive manner (V(max) = 180 pmol/mg/min, K(m) = 189 nM). Membrane vesicles from P-glycoprotein-overexpressing cells showed very low levels of transport. MRP-mediated transport was inhibited by an MRP-specific monoclonal antibody and by a variety of GSH derivatives and cholestatic steroid glucuronides. ATP-dependent transport of unmodified aflatoxin B1 by MRP-enriched membrane vesicles was low but markedly enhanced in the presence of 5 mM GSH, even though GSH conjugates of aflatoxin B1 were not formed by the vesicles. These data demonstrate that MRP is capable of energy-dependent transport of aflatoxin B1 and its GSH conjugates and suggest a potential protective role for MRP in mammalian chemical carcinogenesis.
Assuntos
Transportadores de Cassetes de Ligação de ATP/metabolismo , Trifosfato de Adenosina/farmacologia , Aflatoxina B1/metabolismo , Aflatoxina B1/farmacocinética , Carcinógenos/metabolismo , Carcinógenos/farmacocinética , Glutationa/metabolismo , Glutationa/farmacocinética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Transportadores de Cassetes de Ligação de ATP/genética , Trifosfato de Adenosina/farmacocinética , Transporte Biológico Ativo/efeitos dos fármacos , Carcinoma de Células Pequenas/metabolismo , Cromatografia Líquida de Alta Pressão , Interações Medicamentosas , Resistência a Múltiplos Medicamentos , Glutationa/farmacologia , Humanos , Cinética , Neoplasias Pulmonares/metabolismo , Proteínas Associadas à Resistência a Múltiplos Medicamentos , Mieloma Múltiplo/metabolismo , Estereoisomerismo , Especificidade por Substrato , Trítio , Células Tumorais CultivadasRESUMO
The association between glutathione S-transferase (GST) activity as measured by 1-chloro-2,4-dinitrobenzene (CDNB) conjugation and genotype at exon 5 and exon 6 of the human GSTP1 gene was investigated in normal lung tissue obtained from 34 surgical patients. These samples were genotyped for previously identified polymorphisms in exon 5 (Ile105Val) and exon 6 (Ala114Val) by PCR-RFLP and direct sequencing. GST enzyme activity was significantly lower among individuals with the 105 Val allele. Homozygous Ile/Ile samples (n = 18) had a mean cytosolic CDNB conjugating activity of 74.9 +/- 3.8 nmol/mg per min; heterozygotes (n = 13) had a mean specific activity of 62.1 +/- 4.2 nmol/mg per min and homozygous Val/Val (n = 3) had a mean specific activity of 52.5 +/- 4.5 nmol/mg per min. The CDNB conjugating activity measured for the Ile/Ile genotype group was significantly different from that observed in the Ile/Val group (P = 0.03), and from Ile/Val and Val/Val genotypes combined (P = 0.009). Mean GST activity values were consistently lower in individuals with genotypes containing the 105 valine allele, regardless of smoking exposure. Genotypes at codon 114 were also assessed but the mean GST activity was not significantly lower in individuals with the 114 valine allele. A new haplotype, present in two samples who were homozygous 105Ile and had a 114Val, was identified and proposed as GSTP1*D. Frequencies of the exon 5 and exon 6 polymorphisms were determined in samples obtained from European-Americans, African-Americans and Taiwanese. The differences observed were highly significant suggesting the possibility of GSTP1 genotype-associated, ethnic differences in cancer susceptibility and chemotherapeutic response.
Assuntos
Frequência do Gene , Glutationa Transferase/genética , Pulmão/enzimologia , Grupos Raciais/genética , Povo Asiático/genética , População Negra/genética , Genótipo , Glutationa Transferase/metabolismo , Humanos , Reação em Cadeia da Polimerase , Polimorfismo Genético , Polimorfismo de Fragmento de Restrição , Polimorfismo Conformacional de Fita Simples , Taiwan/epidemiologia , Estados Unidos/epidemiologia , População Branca/genéticaRESUMO
In addition to being a potent hepatocarcinogen, aflatoxin B1 (AFB1) is a pulmonary carcinogen in experimental animals, and epidemiological studies have shown an association between AFB1 exposure and lung cancer in humans. This study investigated AFB1 bioactivation and detoxification in human lung tissue obtained from patients undergoing clinically indicated lobectomy. [3H]AFB1 was bioactivated to a DNA binding metabolite by human whole lung cytosols in a time-, protein concentration-, and AFB1 concentration-dependent manner. Cytosolic activation of [3H]AFB1 correlated with lipoxygenase (LOX) activity and was inhibited by the LOX inhibitor nordihydroguaiaretic acid (NDGA; 100 microM), indicating that LOXs were largely responsible for the observed cytosolic activation of AFB1. In whole lung microsomes, low levels of indomethacin inhibitable prostaglandin H synthase (PHS)-mediated [3H]AFB1-DNA binding and cytochrome P-450 (P450)-mediated [3H]AFB1-DNA binding were observed. Cytosolic glutathione S-transferase (GST)-catalyzed detoxification of AFB1-8,9-epoxide, produced by rabbit liver microsomes, was minimal at 1 and 10 microM [3H]AFB1. With 100 microM [3H]AFB1, [3H]AFB1-8,9-epoxide conjugation with reduced glutathione was 0.34 +/- 0.26 pmol/mg/h (n = 10). In intact, isolated human lung cells, [3H]AFB1 binding to cellular DNA was higher in cell fractions enriched in macrophages than in either type II cell-enriched fractions or fractions containing unseparated cell types. Indomethacin produced a 63-100% decrease in [3H]AFB1-DNA binding in macrophages from five of seven patients, while NDGA inhibited [3H]AFB1-DNA adduct formation by 19, 40 and 56% in macrophages from three of seven patients. In alveolar type II cells, NDGA decreased [3H]AFB1-DNA binding by 30-100% in cells from three patients and indomethacin had little effect. SKF525A, an isozyme non-selective P450 inhibitor, enhanced [3H]AFB1 binding to cellular DNA in unseparated cells, macrophages, and type II cells, suggesting that P450-mediated bioactivation of AFB1 is not a major pathway by which AFB1-8,9-epoxide is formed in human lung cells. Overall, these studies suggest that P450 has a minor role in the bioactivation of AFB1 in human lung. Rather, LOXs and PHS appear to be important bioactivation enzymes. Co-oxidative bioactivation of AFB1, in combination with the low conjugating activity displayed by human lung cytosolic GSTs, likely contributes to human pulmonary susceptibility to AFB1.
Assuntos
Aflatoxina B1/farmacocinética , Carcinógenos/farmacocinética , Pulmão/metabolismo , Aflatoxina B1/análogos & derivados , Aflatoxina B1/metabolismo , Idoso , Animais , Biotransformação , Células Cultivadas , Sistema Enzimático do Citocromo P-450/metabolismo , Citosol/enzimologia , Citosol/metabolismo , Feminino , Glutationa Transferase/metabolismo , Humanos , Inativação Metabólica , Lipoxigenase/metabolismo , Pulmão/enzimologia , Macrófagos Alveolares/enzimologia , Macrófagos Alveolares/metabolismo , Masculino , Microssomos/enzimologia , Microssomos/metabolismo , Pessoa de Meia-Idade , Prostaglandina-Endoperóxido Sintases/metabolismo , Alvéolos Pulmonares/enzimologia , Alvéolos Pulmonares/metabolismo , Coelhos , Frações Subcelulares/enzimologia , Frações Subcelulares/metabolismoRESUMO
Epidemiological studies suggest that aflatoxin B(1) (AFB(1)), a mycotoxin produced by certain Aspergillus species, may play a role in human respiratory cancers in occupationally-exposed individuals. AFB(1) requires bioactivation to the corresponding exo-8,9-epoxide for carcinogenicity, and glutathione S-transferase (GST)-catalyzed conjugation of the epoxide with glutathione (GSH) is a critical determinant of susceptibility to AFB(1). Of the purified human GST enzymes studied, the polymorphic hGSTM1-1 has the highest activity towards AFB(1) exo-epoxide. The influence of the GSTM1 polymorphism on AFB(1)-GSH formation, as well as the abilities of cytosols from preparations enriched in different isolated lung cell types to conjugate AFB(1)-epoxides, were examined. In whole-lung cytosols from patients undergoing clinically indicated lobectomy, GSTM1 genotype correlated with GSTM1 phenotype as determined by [(3)H]trans-stilbene oxide conjugation: GSTM1-positive = 295 +/- 31 pmol/mg/h (n = 6); GSTM1-negative = 92.8 +/- 23.3 pmol/mg/h (n = 4) (P < 0.05). In contrast, conjugation of microsome-generated [(3)H]AFB(1)-epoxides with GSH was low and variable between patients, and did not correlate with GSTM1 genotype: GSTM1-positive = 11.9 +/- 8.1, 111 +/- 66 and 510 +/- 248 fmol/mg/h (n = 6); GSTM1-negative = 15.3 +/- 16.7, 167 +/- 225 and 540 +/- 618 fmol/mg/h (n = 4) (for 1, 10 and 100 microM [(3)H]AFB(1), respectively). GSH conjugates of AFB(1) exo-epoxide and the much less mutagenic stereoisomer AFB(1) endo-epoxide were produced in a ratio of approximately 1:1 in cytosols from both whole lung and isolated cells. Total cytosolic AFB(1)-epoxide conjugation was significantly higher in fractions enriched in alveolar type II cells (3.07 +/- 1.61 pmol/mg/h) than in unseparated lung cells (0.143 +/- 0.055 pmol/mg/h) or fractions enriched in alveolar macrophages (0. 904 +/- 0.319 pmol/mg/h; n = 4) (P < 0.05). Furthermore, AFB(1)-GSH formation and percentage of alveolar type II cells in different cell fractions were correlated (r = 0.78, P < 0.05). These results demonstrate that human lung GSTs exhibit very low conjugation activity for both AFB(1)-8,9-epoxide stereoisomers, and that this activity is heterogeneously distributed among cell types, with alveolar type II cells exhibiting relatively high activity. Of the GSTs present in human peripheral lung which contribute to AFB(1) exo- and endo-epoxide detoxification, hGSTM1-1 appears to play at most only a minor role.