I. Higginson, A. Carr, P. Robinson (eds). Quality of Life

I. Higginson, A. Carr, P. Robinson (eds). BMJ Books, London,2002, 144 pp, $45.00, £24.95, US$39.95 [paperback £24.95,eBook (view only) £14.97, eBook (view and print) £19.96] One week before receiving Quality of Life from the BMJ publishers,I had the opportunity to taste it, downloading/printing a samplechapter and viewing its entirety for only 15     

Height, urban-born and prostate cancer risk in Japanese men

Background: Height and early-life environments have received attention asrisk factors for prostate cancer. However, the evidence is sparsein Japan. To elucidate the associations of height and early-lifefactors with prostate cancer risk in Japanese men, we conducteda hospital-based case–control study. In addition, to investigatewhether the associations vary between prostate cancer and othermajor cancers, we conducted a comparative study within the samecase–control study. Methods: Study subjects consisted of 282 prostate cancer cases, 584,461, 231, and 156 male stomach, lung, colon and rectal cancercases, respectively, and 1730 male hospital controls, aged 50and over admitted to a single hospital in Miyagi Prefecturefrom 1997 to 2003. Information on height and early-life factorsincluding birthplace and stature at 12 years was collected usinga self-administered questionnaire. Odds ratios (ORs) and 95%confidence intervals (95% CIs) were estimated for each exposurevariable. Results: A significant positive association was found between heightand prostate cancer risk (OR, 1.52; 95% CI, 1.00–2.31,between the highest and lowest quartiles; P for trend = 0.03).A significant association of urban-born with prostate cancerrisk was also found (OR, 1.48; 95% CI, 1.03–2.13). Analysesby stage revealed that height might be more strongly associatedwith the risk of advanced prostate cancer. For other major cancers,no significant association with height and early-life factorswas observed. Conclusions: Height and early-life factors were significantly associatedwith prostate cancer risk. Compared with other major cancers,these associations were specific to prostate cancer.     

P53 polymorphisms and haplotypes in lung cancer

An association between the BstU I 1–1 (Pro—Pro)genotype of the p53 codon 72 polymorphism and lung cancer haspreviously been reported by Kawajiri et al. A reanalysis ofthe data by Kawajiri et al. revealed no significant differencebetween patients and controls with respect to allele frequencies,and the increased frequency of BstU 11–1 homozygotes wasmostly ascribable to a deviation from the Hardy—Weinbergequilibrium. In an attempt to replicate the results by Kawajiriet al. we have studied three p53 polymorphisms (BstU I and MspI RFLPs in exon 4 and intron 6 respectively and a 16 bp duplicationin intron 3) and their haplotypes in Swedish lung cancer patientsand controls. The results concerning the codon 72 polymorphismwere largely negative. Thus there was no significant associationbetween lung cancer and the BstU I 1–1 type, and onlya marginal difference (P=0.044) with respect to the BstU I allelefrequency when lung cancer patients were compared with patientswith chronic obstructive pulmonary disease (COPD). However,when the analysis was based on haplotype frequencies largerdifferences appeared and it was found that only BstU I 1 (pro)alleles linked to 16 bp 1 alleles were associated with lungcancer. Pro alleles linked to the 16 bp duplication appearedinstead to confer some protection against cancer. Thus the codon72 alleles need not be functionally involved in lung cancer,but may rather be markers in linkage disequilibrium with othercancer susceptibility sites on p53.     

Absence of p16/MTS1 gene mutations in human prostate cancer

The tumor suppressor gene pl6/MTSl, located on chromosome 9p21,is a cell cycle regulatory gene which is frequently alteredin human cancers. The role of this gene in prostate cancer isunknown. To determine the frequency of deletions and point mutationsof p16/MTS1 in human prostate cancer, we examined 18 cancerand matched benign and hyperplastic tissue specimens. Deletionsof pl6/MTS1 were detected by semi-quantitative multiplex polymerasechain reaction in which a portion of exon 2 of the pl6/MTS1gene and a control marker, the glyceraldehyde 3-phosphate dehydrogenasegene, were amplified simultaneously. ‘Cold’ single-strandedconformational polymorphism (SSCP) analysis was performed toexamine exons 1 and 2 of the pl6/MTS1 gene for point mutations.Our data indicate no evidence for intragenic homozygous deletionin the prostate tumors. One prostate tumor and matched benigntissue showed mobility shifts. Direct DNA sequencing of theSSCP positive samples showed a G     

K.I. Bland, J.M. Daly, C.P. Karakousis (eds). Surgical Oncology: Contemporary Principles and Practice

K.I. Bland, J.M. Daly, C.P. Karakousis (eds). McGraw-Hill, NewYork, NY, 2001, 1223 pp, $220.00, £135, US$175.00 Surgical Oncology: Contemporary Principles and Practice offersin 24 chapters a comprehensive overview of state-of-the-artmanagement of the most common solid     

Relation between benzo[a]pyrene-DNA adducts, cell proliferation and p53 expression in tracheal epithelium of hamsters fed a high {beta}-carotene diet

Vitamin A and ß-carotene protect against respiratorytract cancer by inhibiting the formation of DNA damage and controllingcellular proliferation and differentiation. Recently, it hasbeen shown that the p53 tumor-suppressor gene plays a crucialrole in the etiology of respiratory tract cancer. In the presentstudy, we investigated the relationship between benzo[a]pyrene(B[a]P)-DNA adducts, cell proliferation and p53 expression andthe possible effect of ß-carotene on such a relationshipin tracheal epithelium of hamsters given intratracheal instillationsof B[a]P-Fe₂O₃ particles suspended in saline. DNA-adducts werequantified by the ³²P-postlabeling assay, cell proliferationwas quantified by immunocytochemical detection of incorporatedBrdU during S-phase, and p53 protein was detected by immuno-histochemistrywith an antibody that recognized both the wild-type and themutated protein (BioGenex, Clone BP53–12–1). A clearrelationship appeared to exist between the extent of B[a]P-DNAadduct formation, the induction of cell proliferation and theexpression of p53 protein in hamster tracheal epithelium. Theseresults suggest that B[a]P induces cell proliferation in hamstertracheal epithelial cells most likely by the induction of mutationsin the p53 gene. Furthermore, ß-carotene was not foundto influence the formation of B[a]P-DNA adducts, which is probablydue to the high B[a]P dose. Moreover, ß-carotene didnot statistically significantly affect cell proliferation andp53-protein expression in hamster tracheal epithelial cells.     

Urinary excretion of nitrate, nitrite and N-nitroso compounds in Schistosomiasis and bilharzia bladder cancer patients

Saliva and 24-h urine samples were collected from male Schistosomiasis(bilharzia) patients with S. haematobium infection and possibleconcurrent S.mansoni infection without diagnosed bladder cancer(n = 27), bilharzia patients with diagnosed bladder cancer (n= 23) as well as a comparative control group (n = 27) of healthyEgyptian volunteers with no current bilharzia infection and/orbacterial urinary tract infections from the Nile Delta areaof Egypt. Saliva samples were analysed for the presence of nitrateand nitrite; urine samples were analysed for the presence ofnitrate, nitrite, volatile and non-volatile N-nitroso compounds.Bilharzia patients prior to, and after, diagnosed bladder cancerregularly excreted free nitrite as well as volatile nitrosamines(N-nitrosodimethylamine, N-nitrosodiethylamine, N-nitroso-piperidineand N-nitrosopyrrolidine) in addition to which elevated concentrationsof non-volatile N-nitrosamino acids (N-nitrosoproline, N-nitrososarcosine,N-nitrosothiazolidine-4-carboxylic acid and its 2-methyl derivative)were also present. Total urinary excretion of volatile N-nitrosocompounds (0.32 ± 0.64 µg/day; mean ± SD)and nonvolatile N-nitroso compounds (31.20 ± 22.07 µg/day)was observed in the Egyptian control group. Significantly higherconcentrations were found in bilharzia patients: 3.47 ±6.42 (P < 0.05) and 62.91 ± 21.96 (P < 0.05); aswell as in bilharzia patients with diagnosed bladder cancer:1.71 ± 1.96 (P < 0.02) and 44.94 ± 7.31 respectively.Free nitrite was found in the urine of two volunteers in theEgyptian control group (1.7 and 3.0 µg/day), urinary nitritewas significantly increased in bilharzia patients (5.18 ±9.11 µg/day, P < 0.02) and in bladder cancer patients(1.75 ± 2.81 µg/day, P < 0.05). Nitrate concentrationswere elevated from 139.3 ± 82.2 in the control groupto 143.6 ± 136.3 and 175 ± 190 in the bilharziaand bladder cancer groups respectively. These results indicatethat significant in vivo formation of nitrite and volatile N-nitrosocompounds occurs in the urinary bladder of bilharzia patientsand this may be an oetiological factor in the induction of bilharzialbladder cancer associated with S.haematobium infection.     

Nitrate, nitrite and volatile N-nitroso compounds in the urine of Schistosoma haematobium and Schistosoma mansoni infected patients

The present study presents, for the first time, the amountsof nitrate, nitrite and volatile N-nitroso compounds in salivaand urine samples of Schistosoma haematobium and Schistosomamansoni infected patients. Mid-morning saliva and 24 h urinesamples were collected from male patients infected with S.haematobium(n = 129 saliva and 79 urine samples) and S.mansoni (n = 64saliva and 65 urine samples) and in a comparative control groupof healthy individuals (n = 27) from the Nile Delta region ofEgypt. Saliva samples were analyzed for the presence of nitrateand nitrite; while urine samples were analyzed for the presenceof nitrate, nitrite and volatile N-nitroso compounds. In thecontrol group, N-nitroso-dimethylamine (NDMA) was detected atconcentrations (mean ± SD) of 0.27 ± 0.47 µg/day.N-Nitrosopyrrolidine (NPIP; 0.6 µg/day) and N-nitrosopyrrolidine(NPYR; 0.4 µg/day) were also present in one sample. S.mansoniinfected subjects showed significantly (P < 0.001) higherlevels of 2.9 ± 2.9 µg/day NDMA and a higher frequencyof NPIP (in 40/65 samples; 0.4 ± 0.3 µg/day) andNPYR occurrence (in 59/65 samples; 0.9 ± 0.9 µg/day).Significant further increases in the excretion of volatile N-nitrosocompounds were found in S.haematobium-infected patients withmean daily excretion of 19.2 ± 21 µg/day NDMA (inall samples; P < 0.001), 1.6 ± 2.3 µg/day NPIP(in 56/79 samples; P < 0.001) and 1.3 ± 1.9 µg/dayNPYR (in 58/79 samples; P < 0.1). The differences eitherin salivary nitrite/nitrate or in urinary nitrite between thethree distinct groups were not significant. However, the urinaryexcretion of nitrate was elevated from 139 ± 82mg/dayin the control group to 249 ± 126 mg/day in S.mansoniinfected patients (P < 0.001) and to 174 ± 176 mg/dayin S.haematobium infected subjects (P < 0.005 in comparisonto S.mansoni infected group). These results suggest a possiblerole of N-nitroso compounds in the etiology of schistosome-associatedbladder cancer and imply a partial participation of S.mansoniin the multistage process of urinary schistosomiasis-associatedbladder carcinogenesis.     

Metabolic activation of the potent carcinogen dibenzo[a, l]pyrene by human recombinant cytochromes P450, lung and liver microsomes

The metabolic activation of dibenzo[a, l]pyrene (DB[a, l]P),recently considered the most potent carcinogen among all polycyclicaromatic hydrocarbons, to the 11, 12-dihydrodiol, a precursorof the ultimate carcinogens, the 11, 12-diol-13, 14-epoxides,was investigated using eleven human recombinant cytochrome P450s,as well as human lung and liver microsomes. Of all human P450s,1A1 was the most active in the metabolism of DB[a, l]P (310pmol/min, nmol P450) and had 5–23-fold higher catalyticactivity than other P450s examined. The order of activity inthe formation of the 11, 12-dihydrodiol was as follows: 1A1(116 pmol/min, nmol P450) > 2C9 (29) > 1A2 (22) > 2B6(18) > 3A4 (16) > others (     

Diabetes mellitus and prostate cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

Objective  A history of diabetes has been fairly consistently related to a reduced prostate cancer risk, but previous investigations have not always addressed whether the relation with diabetes varies by prostate cancer aggressiveness or the association between diabetes and prostate cancer is modified by physical activity level and body mass, variables closely related to glucose metabolism. Methods  We prospectively examined the diabetes–prostate cancer risk relationship among 33,088 men in the screening arm of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Results  During 8.9 years follow-up, we ascertained 2,058 incident prostate cancer cases. Diabetes history was related to decreased risk of total prostate cancer (RR = 0.80, 95% CI = 0.68–0.95). The apparent protection afforded by diabetes was primarily due to the inverse relation with non-aggressive disease (i.e., the combination of low grade (Gleason sum <8) and low stage (clinical stages I or II); RR = 0.75; 95% CI = 0.62–0.91). In contrast, no association was noted between diabetes and aggressive disease (i.e., high grade or high stage (Gleason sum ≥8 or clinical stages III or IV); RR = 1.04, 95% CI = 0.74–1.45). In further analyses, the association between diabetes and aggressive prostate cancer was suggestively positive for men who were lean (RR = 1.64, 95% CI = 0.87–3.07; BMI < 25 kg/m²) and it was positive for men who were the most physically active (RR = 1.63; 95% CI = 1.07–2.62; 3+ hours vigorous activity/week). By comparison, no relations of diabetes to aggressive prostate cancer were noted for their heavier or physically less active counterparts (p-value for tests of interaction = 0.10 and 0.03 BMI and physical activity, respectively). Conclusion  In this study, diabetes showed divergent relations with prostate cancer by tumor aggressiveness. Specifically, diabetes was inversely associated with early stage prostate cancer but it showed no relation with aggressive prostate cancer. Exploratory analyses suggested a positive association between diabetes and aggressive prostate cancer in the subgroup of men with a low BMI.     

Comparative tumorigenicity of benzo[a]pyrene, 1-nitropyrene and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine administered by gavage to female CD rats

Agents that are ubiquitous in the environment and are knowninducers of mammary cancer in rodents can be regarded as potentialcauses of human cancer and need to be evaluated more completely.Therefore, the purpose of this study was to determine underidentical conditions the relative carcinogenic potency in themammary glands of rats of benzo[a]pyrene (B[a]P), 1-nitropyrene(1-NP) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyidne (PhIP).Thirty-day-old female CD rats were gavaged once weekly for 8weeks with B[a]P, 1-NP or PhIP. Each compound was given at 50µmol/rat/week in 0.5 ml trioctanoin for a total dose of400 µmoul/rat. Forty-one weeks after the last carcinogenadministration, rats were killed. In the 1-NP-treated rats,treatment elicited primarily benign tumors. In contrast, theB[a]P- and PhIP-treated rats developed both malignant and benigntumors. The incidence of adenocarcinomas in rats treated withB[a]P or PhIP was comparable and significantly higher than thatin animals receiving trioctanoin only. The incidence of benigntumors (fibroadenomas, desmoplastic adenomas and adenomas) observedin animals treated with B[a]P or 1-NP was comparable and significantlyhigher than that in animals given PhIP or trioctanoin. Thisis the first report describing the carcinogenic activity ofPhIP, given by gavage, in the mammary gland of CD rats and rankingthe carcinogenic potency observed under identical conditions,of three agents (B[a]P     

Plasma levels of prothrombin fragment F1+2, D-dimer and prothrombin time correlate with clinical stage and lymph node metastasis in operable gastric cancer patients

Objective: The principal objective of this study was to determine the relationshipbetween preoperative coagulation tests and the extent of tumorinvolvement in gastric cancer patients. Method: A total of 110 patients with adenocarcinoma of the stomach werestudied in order to evaluate this relationship. Platelet count(P), prothrombin time (PT), activated partial thromboplastintime, D-dimer, fibrinogen degradation product, thrombin–antithrombincomplex and prothrombin fragment F1+2 (F1+2) were evaluated. Results: The D-dimer levels were positively correlated with the depthof invasion (P =0.007). Plasma D-dimer and PT were highly correlatedwith degree of lymph node involvement (P = 0.006, 0.004, respectively).D-dimer level, PT and plasma F1+2 level were correlated withclinical stage (P = 0.001, 0.017, 0.031, respectively). PT andF1+2 levels were significant in the prediction of the presenceof lymph node involvement on the multivariate logistic regressionmodels (odds ratio 2502.081 (5.977–1047425.4); P = 0.010and odds ratio 19.487 (1.495–253.936); P = 0.023, respectively). Conclusion: PT and plasma levels of F1+2 and D-dimer could be markers ofdegree or presence of lymph node involvement and clinical stagein patients with operable gastric cancer.     

Reply to 'Not credible: a subversion of science by the pharmaceutical industry. Commentary on A global comparison regarding patient access to cancer drugs (Annals of Oncology 2007, vol 18, Suppl 3, pp1-75)' by Michel P Coleman

Declaration of interest: All authors have received researchgrants and honoraria for lectures and advisory from the pharmaceuticalindustry at different occasions, including funding from Rochefor the study A Global comparison regarding patient access tocancer drugs. Professor Coleman wrongly states that the key question addressedin our report is ‘whether national cancer survival isassociated with national cancer drug licensing’. Thatexplains his comments, but also reveals that he has no interestin, or contribution to, the main issues addressed: how doespatients' access to cancer drugs vary between countries, whatare the explanations for this variation, and what are the possiblepolicy responses at national and international levels. In particularwe are interested in the impact of health technology     

Descriptive epidemiology of vulvar and vaginal cancers in Vaud, Switzerland, 1974-1994

Background: To analyse trends in incidence, survival and riskof second neoplasms following vaginal and vulvar cancers usingdata collected by the Swiss Cancer Registry of Vaud over the21-year period 1974–1994. Materials and methods: Subjects were 257 vulvo-vaginal cancers.Of these, 69 were vaginal, 153 vulvar cancers, and 35 non-specifiedlower genital tract neoplasms; 94 in situ neoplasms were alsoregistered (85 for the vulva). Results: Invasive vaginal cancer incidence decreased from 0.8in 1974–1984 to 0.4/100,000 women in 1985–1994,while invasive vulvar cancer incidence remained approximatelystable around 1.2/100,000 (world standard); incidence of insitu vulvar cancer increased from 0.8 to 1.3/100,000, the risebeing larger in younger women. Significant excesses for secondprimary neoplasms were observed for oro-pharyngeal and lungcancer, and for non-melanomatous skin neoplasms, as well asfor invasive vulvar cancers following in situ cancers. Conclusions: This population-based dataset confirms that theincidence of in situ vulvar (but not invasive vulvar or vaginalcancer) has been increasing over the last 20 years. The excesssecond primary neoplasms supports the hypotheses that humanpapillomavirus and cigarette smoking are related to vulvo-vaginalneoplasms. epidemiology, incidence, multiple tumours, neoplasms, survival, time trends, vagina, vulva     

The presence of mutagens/carcinogens in the excised lung and analysis of lung cancer induction

To elucidate a relationship between lung cancer and tumor inductionof environmental chemicals, the presence of 1-nitropyrene (1-NP)and benzo[a]pyrene (B[a]P) in 137 Japanese (97 male and 40 female),and 21 Chinese lung specimens was examined by HPLC, and GC–MSand environmental exposure discussed. Mortality due to lungcancer in Fuyuan County, China, is much higher than that ofother cancers. We investigated 21 patients who were residentsof Fuyuan County. All were female aged 28–64 years andwere non-smoking farmers and cooks. The histological featuresof the tumors were adenocarcinoma, squamous cell carcinoma andsmall cell carcinoma. The incidence of cancer was due to inhalingsoot from the combustion of coal used for cooking and indoorheating. The polycyclic aromatic hydrocarbons, chrysene, benzo[k]fluor-anthene,B[a]P, benzo[g,h,i]perylene and pyrene, but not their nitratedderivatives, were detected in substantial amounts in the resectedlungs. These mutagens and carcinogens normally originate incombustion products of coal, and are discussed as the possibleinitiators of the tumors in the lungs of these patients. Allthe Japanese lung specimens were also obtained from non-smokers.The concentrations of 1-NP averaged 21.3 ± 12.4 and 5.9± 2.4 pg/g of Japanese and Chinese samples respectively.The concentrations of B[a]P averaged 180.2 ± 103.7 and608.7 ± 477.1 pg/g of Japanese and Chinese samples respectively.Thus, Japanese and Chinese lung specimens were mainly contaminatedby 1-NP and B[a]P, respectively. Typical tissues from a carcinomatoushuman lung were examined. The patient was a 64-year-old Japanesemale non-smoker and farmer who had raised chickens over a periodof 40 years. The histological features of the tumor were thoseof keratinizing squamous cell carcinoma. 1-Nitropyrene, 1-nitro-3-hydroxypyrene,1,3-dinitropyrene and chrysene were detected at concentrationsof 0.11, 0.036, 0.095 and 0.16 ng respectively per gram of lungtissue. This cancer was due to long-term exposure to the combustionproducts of heavy oil used in a chicken house.     

p53 polymorphisms and haplotypes in breast cancer

Three polymorphisms in the human tumor suppressor gene p53 (BstUIand MspI RFLPs in exon 4 and intron 6 respectively and a 16bp duplication in intron 3) and their haplotype combinationswere studied in patients with breast cancer and controls. Asignificant increase in the codon 72 BstUI A1 (pro) allele frequency(p= 0.016) and of individuals carrying the pro allele (pro/proand pro/arg) (OR,1.47; p = 0.014; 95% CI, 1.08–2.00) wasobserved in breast cancer. This increase wasmost pronouncedin highly differentiated breast cancer. Significant associationswere found only in BstUIand haplotypes containing this polymorphism,which indicates that the codon 72 pro allele may be functionallyinvolved in low malignancy breast cancer. The distributionsof genotypic combinations in breast cancer patients and controlswere significantly different (p = 0.005). Two BstUI–16bp-MspI combinations were significantly overrepresented; 2–1,1–1, 2–2 (OR, 1.61; 95% CI, 1.13–2.30) and1–1, 2–1, 2–1 (OR, 2.94; 95% CI, 1.37–6.27).     

SHORT COMMUNICATION: Influence of a mutation reducing the catalytic activity of the cytochrome P450 CYP2D6 on lung cancer susceptibility

The possible association between lung cancer and the CYP2D6*9mutant allele, which reduces the catalytic activity of cytochromeP450 CYP2D6, was examined by PCR-SSCP using peripheral bloodDNA from 249 cases of lung cancer and 265 controls, with detaileddata on smoking. The CYP2D6*9 mutant allele was present in 4.9%of controls and 6% of cases. Adjusted for age, hospital andsmoking, the odds ratio (OR) of lung cancer associated withthe presence of the CYP2D6*9 mutant allele was 12 [95% confidenceinterval (CI) 0.5–2.9]. According to histological type,adenocarcinoma and small cell carcinoma were not associatedwith the presence of the CYP2D6*9 mutant allele and a non-significanthigher occurence of the mutant allele was observed for squamouscell carcinoma (OR 1.74, 95% CI 0.6–4.8). Moreover, noassociations were observed upon stratification by number ofpack-years of cigarette smoking. These results do not confirman earlier report that this CYP2D6*9 mutant allele may be anadditional risk factor for the development of lung cancer.     

Identification of the cytochrome P450 isozymes involved in the metabolism of N-nitrosodipropyl-, N-nitrosodibutyl- and N-nitroso-n-butyl-n-propylamine

The metabolism of N-nitrosodipropylamine (NDPA), N-nitrosodibutylamine(NDBA) and N-nitroso-n-butyl-n-propylamine (NBPA) was investigatedin vitro using liver microsomes and purified isoforms of cytochromeP450 in a reconstituted system. Liver microsomes were preparedfrom rats pretreated with phenobarbital (PB), pyridine (PYR),ß-naphthoflavone (BNF), butylated hydroxytoluene (BHT),butylated hydroxyanisole (BHA), clofibrate (CLO) or from untreatedrats. The purified cytochrome P450s used in the reconstitutedsystem were rat 1A1 and 2B1and rabbit 2E1. The rates of metabolismand the product profiles for NDPA, NDBA and NBPA changed significantlydepending on the pretreatment of the rats or the identity ofthe purified cytochrome P450 isoforms. Induction by PB dramaticallyincreased cleavage of NDPA, NDBA and NBPA at C-N bonds, leadingto substantial increases in formation of the respective aldehydesand the overall metabolic rates. Microsomes from PYR-pretreatedrats exhibited increased activities for formation of formaldehydeand propionaldehyde from NDPA and NBPA. Microsomes from BHT-pretreatedrats showed a slight increase in activity for N-dealkylationof NDBA and NBPA. Treatment with BHA decreased the overall metabolismof NDBA, but slightly increased N-dealkylation of NBPA. Microsomalmetabolism of NDPA, NDBA and NBPA was decreased by pretreatmentwith BNF and CLO. Results from studies using the reconstitutedsystem with purified cytochrome P450 isoforms demonstrated thatcytochrome P450 2B1 specifically catalyzed     

B.W.S. Robinson, A.P. Chahinian (eds). Mesothelioma

B.W.S. Robinson, A.P. Chahinian (eds). Martin Dunitz Ltd, London,2002, 380 pp, £95.00, US$145.00 The incidence of mesothelioma is approaching its peak, and theprognosis for this cancer remains extremely poor. The impossibilityof predicting cancer appearance after asbestos exposure, thedifficulty of     

Persistence, gestation stage-dependent formation and interrelationship of benzo[a]pyrene-induced DNA adducts in mothers, placentae and fetuses of Erythrocebus patas monkeys

Since DNA adducts have been detected in the placentae of pregnantwomen who smoke cigarettes, the importance of these adductsas biomarkers of fetal exposure and risk has been evaluatedusing a non-human primate as a model. Pregnant Erythrocebuspatas monkeys on days 50, 100 or 150 of gestation (term = 160± 5 days) were treated once with 5–50 mg/kg benzo[a]pyrene(B[a]P), p.o. Fetuses were removed by Cesarean section 1–50days after treatment and analyzed for DNA adducts by the nucleaseP₁ version of the ³²P-postlabeling method. B[a]P induced highlevels of DNA adducts in all fetal organs, placentae and maternallivers in all three trimesters of gestation. DNA adduct levelswere higher in mid-gestation compared to early and late gestation.The major adduct detected was 10ß-(deoxyguanosin)-N²-yl-7ß,8