Epidemiology of periodontal disease in dogs in the UK primary-care veterinary setting.

OBJECTIVES: Periodontal disease is a frequent diagnosis of dogs and can have severe negative impacts on welfare. It was hypothesised that breeds with skull shapes that differ most in conformation from the moderate mesocephalic skull shape have higher odds of periodontal disease. MATERIALS AND METHODS: The cohort study included a random sample of dogs under primary veterinary care in 2016 from the VetCompass Programme database. Risk factor analysis used random effects multivariable logistic regression modelling. RESULTS: The study included a random sample of 22,333 dogs. The 1-year period prevalence for diagnosis with periodontal disease was 12.52% (95% CI: 12.09 to 12.97). Eighteen breeds showed increased odds compared with crossbred dogs. Breeds with the highest odds included Toy Poodle (odds ratio 3.97, 95% confidence intervals 2.21 to 7.13), King Charles Spaniel (odds ratio 2.63, 95% confidence interval 1.50 to 4.61), Greyhound (odds ratio 2.58, 95% confidence interval 1.75 to 3.80) and Cavalier King Charles Spaniel (odds ratio 2.39, 95% confidence interval 1.85 to 3.09). Four breeds showed reduced odds compared with crossbreds. Brachycephalic breeds had 1.25 times the odds (95% confidence interval 1.11 to 1.42) of periodontal disease compared with mesocephalic breeds. Spaniel types had 1.63 times the odds (95% confidence interval 1.42 to 1.87) compared with non-spaniel types. Increasing adult bodyweight was associated with progressively decreasing odds of periodontal disease. CLINICAL SIGNIFICANCE: The high prevalence identified in this study highlights periodontal disease as a priority welfare concern for predisposed breeds. Veterinarians can use this information to promote improved dental care in predisposed dogs, especially as these dogs age.

Discrete-time semi-Markov modeling of human papillomavirus persistence.

Multi-state modeling is often employed to describe the progression of a disease process. In epidemiological studies of certain diseases, the disease state is typically only observed at periodic clinical visits, producing incomplete longitudinal data. In this paper we consider fitting semi-Markov models to estimate the persistence of human papillomavirus (HPV) type-specific infection in studies where the status of HPV type(s) is assessed periodically. Simulation study results are presented indicating that the semi-Markov estimator is more accurate than an estimator currently used in the HPV literature. The methods are illustrated using data from the HIV Epidemiology Research Study.

Why the null matters: statistical tests, random walks and evolution.

A number of statistical tests have been developed to determine what type of dynamics underlie observed changes in morphology in evolutionary time series, based on the pattern of change within the time series. The theory of the 'scaled maximum', the 'log-rate-interval' (LRI) method, and the Hurst exponent all operate on the same principle of comparing the maximum change, or rate of change, in the observed dataset to the maximum change expected of a random walk. Less change in a dataset than expected of a random walk has been interpreted as indicating stabilizing selection, while more change implies directional selection. The 'runs test' in contrast, operates on the sequencing of steps, rather than on excursion. Applications of these tests to computer generated, simulated time series of known dynamical form and various levels of additive noise indicate that there is a fundamental asymmetry in the rate of type II errors of the tests based on excursion: they are all highly sensitive to noise in models of directional selection that result in a linear trend within a time series, but are largely noise immune in the case of a simple model of stabilizing selection. Additionally, the LRI method has a lower sensitivity than originally claimed, due to the large range of LRI rates produced by random walks. Examination of the published results of these tests show that they have seldom produced a conclusion that an observed evolutionary time series was due to directional selection, a result which needs closer examination in light of the asymmetric response of these tests.

Effects of plant species richness on invasion dynamics, disease outbreaks, insect abundances and diversity.

Declining biodiversity represents one of the most dramatic and irreversible aspects of anthropogenic global change, yet the ecological implications of this change are poorly understood. Recent studies have shown that biodiversity loss of basal species, such as autotrophs or plants, affects fundamental ecosystem processes such as nutrient dynamics and autotrophic production. Ecological theory predicts that changes induced by the loss of biodiversity at the base of an ecosystem should impact the entire system. Here we show that experimental reductions in grassland plant richness increase ecosystem vulnerability to invasions by plant species, enhance the spread of plant fungal diseases, and alter the richness and structure of insect communities. These results suggest that the loss of basal species may have profound effects on the integrity and functioning of ecosystems.

Alterations in the K-ras and p53 genes in rat lung tumors.

Activation of the K-ras protooncogene and inactivation of the p53 tumor suppressor gene are events common to many types of human cancers. Molecular epidemiology studies have associated mutational profiles in these genes with specific exposures. The purpose of this paper is to review investigations that have examined the role of the K-ras and p53 genes in lung tumors induced in the F344 rat by mutagenic and nonmutagenic exposures. Mutation profiles within the K-ras and p53 genes, if present in rat lung tumors, would help to define some of the molecular mechanisms underlying cancer induction by various environmental agents. Pulmonary adenocarcinomas or squamous cell carcinomas were induced by tetranitromethane (TNM), 4-methylnitrosamino-1-(3-pyridyl)-1-butanone (NNK), beryllium metal, plutonium-239, X-ray, diesel exhaust, or carbon black. These agents were chosen because the tumors they produced could arise via different types of DNA damage. Mutation of the K-ras gene was determined by approaches that included DNA transfection, direct sequencing, mismatch hybridization, and restriction fragment length polymorphism analysis. The frequency for mutation of the K-ras gene was exposure dependent. Only two agents, TNM and plutonium, led to mutation frequencies of > 10%. In both cases, the transition mutations formed could have been derived from deamination of cytosine. The identification of non-ras transforming genes in rat lung tumors induced by mutagenic and nonmutagenic exposures such as NNK and beryllium would help define some of the mechanisms underlying cancer induction by different types of DNA damage. Alteration in the p53 gene was assessed by immunohistochemical analysis for p53 protein and single-strand conformation polymorphism (SSCP) analysis of exons 4 to 9. None of the 93 adenocarcinomas examined was immunoreactive toward the anti-p53 antibody CM1. In contrast, 14 to 71 squamous cell carcinomas exhibited nuclear p53 immunoreactivity with no correlation to type of exposure. However, SSCP analysis only detected mutations in 2 of 14 squamous cell tumors that were immunoreactive, suggesting that protein stabilization did not stem from mutations within the p53 gene. Thus, the p53 gene does not appear to be involved in the genesis of most rat lung tumors.

Induction of genomic instability in normal human bronchial epithelial cells by 238Pu alpha-particles.

Pulmonary deposition of alpha-particle-emitting radon daughters is estimated to account for 10% of all lung cancer deaths in the USA. However, the nature and timing of early (preneoplastic) genetic alterations in radon-associated lung cancer are still relatively uncertain. The purpose of this investigation was to determine whether genomic instability occurs after exposure of cultured normal human bronchial epithelial cells to six equal, fractionated doses of alpha-particles (total doses 2-4 Gy). Two weeks after the final exposure, foci of phenotypically altered cells (PACs) were detected in 0, 63 and 77% of control, low and high dose cultures respectively. Of these, 18% exhibited extended life spans relative to unexposed controls. Elevated frequencies of binucleated cells (BNCs), a marker of genomic instability, were observed in 60 and 38% of the PAC cultures from the low and high dose groups respectively. The micronucleus assay also showed evidence of genomic instability in 40 and 38% of PAC cultures from the low dose and high dose groups respectively. No changes in microsatellite length, another marker of genomic instability, were detected in any of the PAC samples with the 28 markers used for this assay. However, one PAC (L2) showed a hemizygous deletion at 9p13.3. Another PAC (H9), which exhibited the highest frequency of cells containing micronuclei (MN), exhibited a hemizygous deletion at 7q31.3. Each loss may represent a stable mutation that resulted either directly from irradiation or later in progeny of exposed cells because of alpha-particle-induced genomic instability. The fact that elevated levels of BNCs and MN were present in the progeny many generations after irradiation indicates that the genetic alterations detected with these two markers were not a direct consequence of radiation exposure, but of resulting genomic instability, which may be an early change after exposure to alpha-particles.

Low frequency of alterations in p53, K-ras, and mdm2 in rat lung neoplasms induced by diesel exhaust or carbon black.

Inhalation of diesel exhaust (DE), which contains soot particles with adsorbed mutagenic organic compounds, and its virtually mutagen-free soot particle analog, carbon black (CB), produce similar types and prevalences of pulmonary neoplasms in chronically exposed F344 rats. This result suggests that DE-induced neoplasia develops from the effects of a high lung burden of carbonaceous particles rather than from the genotoxicity of organic constituents. In this investigation, pulmonary carcinomas from rats exposed to DE or CB were analyzed for alterations in K-ras and p53 to determine if mutations caused by these agents are also similar. K-ras and p53 were chosen for this study because mutation patterns of these genes in lung neoplasms have been associated with specific exposures. A low frequency (3/50) and variable pattern of activating mutations were identified in codons 12 and 61 of the K-ras gene. Immunoreactive levels of p53 protein, suggesting gene dysfunction, were present in 7/13 squamous cell or adenosquamous carcinomas, regardless of the associated exposure. However, single-strand conformational polymorphism analysis and direct sequencing of p53 did not detect any mutations in these neoplasms. No immunoreactivity or mutations in p53 were observed in adenocarcinomas. The increased level of p53 protein in the squamous carcinomas is not explained by stabilization by the mdm2 gene product, because this protein was not overexpressed based on immunohistochemical analysis. No pattern of mutation was detected that would suggest a differential mechanism of carcinogenicity between DE and CB; however, inactivation of the p53 pathway may have a role in the development of rat lung neoplasms with a squamous cell carcinoma component.

Detection and quantitation of mutant K-ras codon 12 restriction fragments by capillary electrophoresis.

Polymerase chain reaction amplification and BstNI endonuclease digestion were performed on DNA isolated from cell lines that were either homozygous (SW480, A549) or heterozygous (Calu 1, SK-LU-1, A427) for K-ras codon 12 mutations. Polyacrylamide gel electrophoresis showed that both mutant and wildtype (WT) bands were present in Calu-1, SK-LU-1, and A427 cell DNA; only the mutant bands were observed with SW480 and A549 DNA. The percentages of mutant and WT fragments were measured using capillary electrophoresis (CE). Integration of mutant and WT peaks showed that the percentages of mutant alleles in Calu-1, SK-LU-1, and A427 cell lines were 73, 84, and 72, respectively. The sensitivity of the original BstNI assay for K-ras codon 12 in conjunction with analysis by CE was also tested by a series of titration experiments using one- and two-stage amplification-BstNI digestion protocols. CE was used to generate a calibration curve. The mutant allele was detected and the quantity was measured in the 1:100 and 1:10,000 dilutions in the one- and two-stage analysis, respectively. Four human lung adenocarcinomas were also analyzed. Two of these were homozygous normal, whereas the other two contained 63 and 32% codon 12 mutant alleles. These results showed that CE can separate and quantitate BstNI fragments containing K-ras codon 12 mutations. The high sensitivity and quantitative features of CE should enable detection and quantitation of mutant K-ras alleles in premalignant lung lesions, as well as exfoliated cells collected by cytology from persons at risk for lung cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Preampullary congenital duodenal obstruction in a father and son.

This is the report of an infant seen on June 25, 1960 with preampullary total duodenal obstruction caused by a combined annular pancreas and duodenal stenosis above the ampulla. A gastroduodenostomy was performed. In December 1989, he fathered a 1,700-g boy with preampullary duodenal atresia. A duodeno-duodenostomy was performed successfully by the same pediatric surgeon. Second-generation duodenal obstruction is rare; to our knowledge, there are no other cases.

Metabolism of nitrofluoranthenes by rat lung subcellular fractions.

The nitrofluoranthene (NF) family of compounds includes the potent pulmonary carcinogen 3,9-dinitrofluoranthene (3,9-DNF) and the weak carcinogen 3-nitrofluoranthene (3-NF). Although the specific molecular mechanisms involved in this difference in sensitivity for the induction of lung tumors in rats by 3,9-DNF and 3-NF have not been defined, these compounds most likely induce carcinogenesis by metabolic activation to electrophilic metabolites that bind DNA. The purpose of these investigations was to determine the activation pathways in the rat lung for the metabolism of the di-(3,9-DNF) and mono-nitroisomers (3-NF, 8-NF, 2-NF) of NFs. The metabolic rates of NFs were compared for lung subcellular fractions of pristine rats as well as rats previously treated with 3-methylcholanthrene (3-MC) or phenobarbital at levels that would induce cytochrome P450 enzymes. One major metabolite, the amino derivative, was detected by high pressure liquid chromatography following anaerobic incubation of rat lung cytosol with 3-NF, 8-NF, 2-NF or 3,9-DNF. 3,9-DNF was metabolized to its amino derivative, aminonitrofluoranthene, at a higher rate than 3-NF, 8-NF or 2-NF. Pretreatment of the rats with 3-MC or phenobarbital did not affect the metabolic rates of cytosolic reduction. Both 3-NF and 3,9-DNF were metabolized anaerobically to their amino derivatives by microsomal reductas(s). 3,9-DNF was metabolized twice as fast as 3-NF. The formation of the aminonitrofluoranthene metabolite was increased approximately 2 times with microsomes from 3-MC-induced rats, but was unaffected by microsomes from phenobarbital-treated rats. This suggests that the cytochrome P450 isozymes and reductase, which are induced by 3-MC, may be involved in the metabolism of 3-NF and 3,9-DNF. The metabolic products of 3-NF, formed aerobically, consisted of one major and three minor compounds. The major metabolite, tentatively identified as 3-NF-8-ol, was increased approximately 6 times using microsomes from 3-MC-induced rats. In contrast, 3,9-DNF metabolism was not detected aerobically with lung microsomes. Thus, ring hydroxylation was inhibited in the metabolism of 3,9-DNF, and the major pathway was nitroreduction. This higher rate of anaerobic metabolism of 3,9-DNF over 3-NF and the expected high reactivity of the putative N-acetoxy derivative formed from 3,9-DNF may be responsible for the differential potency for lung cancer induction by these two carcinogens.

Chemical carcinogen-induced damage to the c-neu and c-myc protooncogenes in rat lung epithelial cells: possible mechanisms for differential repair in transcriptionally active genes.

N-methyl-N'-nitro-N-nitrosoguanidine (M-NNG)-induced damage to two transcriptionally active genes, c-neu and c-myc, was studied in rat lung epithelial cells in vitro. MNNG, a direct acting alkylating agent that produces alkalilabile sites in DNA, caused damage to both protooncogenes. DNA damage was determined by monitoring the disappearance of specific fragments generated by restriction enzyme digestion in Southern blots. DNA repair in the c-neu and c-myc protooncogenes was examined in confluent cells by measuring the reappearance of these same bands. While the c-neu gene exhibited repair in 24 h, none was detected in the c-myc gene. These results imply that the promutagenic DNA lesions caused by MNNG are differentially repaired in two transcriptionally active genes.

Cytotoxic and transformation responses of rat tracheal epithelial cells exposed to nitrated polycyclic aromatic hydrocarbons in culture.

Four nitropolycyclic aromatic hydrocarbons (NPAHs) were investigated for their cytotoxic effects on rat tracheal epithelial (RTE) cells. 6-Nitrochrysene (6-NC), 1,6-dinitropyrene (1,6-DNP), 1-nitropyrene (1-NP) and 4-nitropyrene (4-NP) induced dose-dependent decreases in the relative colony-forming efficiency (RCFE) of RTE cells. The compounds could be separated into two groups based on their cytotoxic potencies, a group that displayed high cytotoxic effects (6-NC and 1,6-DNP), and a group that displayed low cytotoxic effects (1-NP and 4-NP). The most cytotoxic compound was 6-NC, with an ED50 of 0.13 microM, followed by 1,6-DNP, 4-NP and 1-NP with ED50s of 1.25, 8.9 and 9.1 microM, respectively. The most cytotoxic compound (6-NC) and one of the components with low cytotoxicity (1-NP) were assayed for their ability to induce preneoplastic transformation of RTE cells using equally toxic doses of both compounds. The frequencies of transformation induced by 6-NC in cells isolated from control animals or from animals pretreated with 3-methylcholanthrene (3-MC) were 8.4 X 10(-3) and 21.4 X 10(-3), respectively. 1-NP did not induce cell transformation. Equally toxic doses of the direct acting carcinogen N-methyl-N'-nitro-N-nitrosoguanidine, used as a positive control, induced transformation frequencies of 8.7 X 10(-3) and 6.4 X 10(-3) in cells isolated from control animals or from animals pretreated with 3-MC, respectively. These studies show that RTE cells have the metabolic capacity to activate NPAHs to toxic metabolites; thus, the RTE system should be very useful for evaluating the potential toxic effects of this ubiquitous class of airborne pollutants. In addition, the observed differences in cellular toxicity and transformation capabilities of 6-NC and 1-NP were consistent with the results of other studies that demonstrated the greater potency for induction of tumors in animals of 6-NC relative to 1-NP.

Development or restoration of trust in interpersonal relationships during adolescence and beyond.

Individuals low in interpersonal trust have been found to be less confident, less popular with others, and more lonely--all indicators of a need for attitudinal and behavioral change. A student who has reached a point of sufficient discomfort to seek therapeutic assistance can be aided in increasing trust in others through specific tasks cooperatively established by the counselor or other helping professional.

Binding of polycyclic and nitropolycyclic aromatic hydrocarbons to specific fractions of rat lung chromatin.

Carcinogen-induced damage to nuclear matrix DNA, the site of DNA replication and transcription, could have profound effects on gene regulation and mutation. 1,6-Dinitropyrene (1,6-DNP), 1-nitropyrene (1-NP), 6-nitrobenzo[a]pyrene (6-NBP), benzo[a]pyrene (BP) and benzo[a]pyrene diolepoxide (BPDE) were investigated for their abilities to bind to selected regions of DNA in rat lung cell nuclei. Following in vitro exposure to carcinogen, nuclei were fractionated into active chromatin (AC), nuclear matrix (NM) and bulk (low and high salt) chromatin fractions. At an equivalent molar concentration, the highest binding to unfractionated (total) DNA was obtained with BPDE, followed in order by BP, 1,6-DNP, 6-NBP and 1-NP. BPDE, a direct alkylating compound, was bound approximately 18 times higher than the other compounds. All compounds were bound to AC (mononucleosomal DNA approximately 185 bp) and to NM in greater amounts than to bulk DNA. The binding ratios (AC + NM)/(LS + HS) varied from 2 to 21, depending upon the compound. The selective binding to specific DNA regions did not appear to be significantly related to the structures of the parent compounds or to their inferred metabolites. Thus, it appears that selective binding to specific regions is a general phenomenon that is related to the open state of the chromatin structure.

Factors affecting possible carcinogenicity of inhaled nitropyrene aerosols.

Nitroaromatics in general, and 1-nitropyrene in particular, are potent bacterial mutagens and animal carcinogens. Their importance as possible human carcinogens is difficult to assess because they are usually found in the environment as the products of combustion processes, and so they usually exist with many other compounds associated with airborne particles. The experiments reported here were carried out to determine if the inhalation of particle-associated 1-nitropyrene, or the concomitant exposure to an irritant gas, would alter the tissue distribution of 1-nitropyrene or its metabolites, compared to their distribution after inhalation of pure 1-nitropyrene. These experiments were intended to yield insights into the mechanisms involved in the potential carcinogenicity of particle-associated nitroaromatics as inhaled in the environment from automotive emissions and other sources. Groups of Fischer 344 rats inhaled pure 14C-1-nitropyrene aerosols, with and without coexposure to 5 parts per million sulfur dioxide, or 14C-1-nitropyrene adsorbed onto gallium oxide particles, with and without coexposure to sulfur dioxide, for four weeks. Lung retention of 14C-1-nitropyrene was not prolonged by its association with gallium oxide particles or by coexposure to sulfur dioxide. There was a marked inflammatory and fibrogenic response to the gallium oxide particles. Another set of experiments was carried out in which rats were exposed to 14C-1-nitropyrene either as pure aerosol or adsorbed onto carbon black particles. The amount of 14C in the lung that was bound to carbon black particles steadily decreased with time after exposure, compared to total lung 14C, indicating removal of 14C from the particles. Thirty minutes after exposure, the amount of 14C covalently bound to lung macromolecules, expressed as a percentage of calculated deposited radioactivity, was twofold greater for 1-nitropyrene adsorbed onto carbon black than for 1-nitropyrene alone. The amount of covalently bound 14C increased with time after exposure to 14C-1-nitropyrene adsorbed onto carbon black, reaching a level of approximately 1 percent of deposited radioactivity, 10-fold greater than that seen with pure 14C-1-nitropyrene seven to 30 days after exposure. The level of covalently bound 14C declined steadily after exposure to pure 14C-1-nitropyrene. Carbon black particles associated with adsorbed 1-nitropyrene offer the potential of studying DNA adduct formation in the lung, because DNA modification might be greater after inhalation of 1-nitropyrene adsorbed onto carbon black than after inhalation of pure 1-nitropyrene or 1-nitropyrene associated with metal oxides, such as gallium oxide.(ABSTRACT TRUNCATED AT 400 WORDS)

Damage and repair of mouse lung DNA induced by 1-nitropyrene.

The induction of DNA single-strand breaks (SSB), the repair of SSB, and the role of cell turnover in the removal of SSB were determined in mouse lung following intratracheal instillation of 1-nitropyrene (1-NP). Cellular DNA was prelabeled with [3H]thymidine in neonate and adult mice. 1-NP was administered to labeled neonate mice after they became adults and to the adult mice that were labeled when adults. 1-NP induced a dose-related increase in SSB (10-22 times control rate) as early as 2 h after 1-NP administration. The mice labeled as neonates were more sensitive to SSB induction by 1-NP and had a faster repair rate than mice labeled when adults. By one week after 1-NP administration, the levels of SSB in both groups of mice were similar to controls. The half-lives for DNA turnover in mice prelabeled as neonates and in mice prelabeled when adults were approximately 22 and approximately 9 days, respectively, at the time of 1-NP treatments. These data indicate that both highly proliferative cell populations and populations with lower rates of proliferation are amenable to 1-NP-induced DNA lesions. The rate of cell DNA turnover suggests that active DNA repair processes are involved in the removal of DNA lesions. The slower rate of DNA repair coupled with a relatively high rate of cell division in the rapid proliferative cells suggest that these cells may be involved in the induction of cancer in animals after 1-NP administration.

Formation of DNA adducts in mouse tissues after intratracheal instillation of 1-nitropyrene.

1-Nitropyrene (1-NP), a ubiquitous environmental pollutant, is a mammalian mutagen and causes cancer in animals. The ability of the lung, liver and kidney to form 1-NP-DNA adducts was determined in adult male B6C3F1 mice following a single intratracheal instillation of 1-NP. 1-NP-DNA adducts were isolated and characterized in mouse lung, liver and kidney by HPLC analysis of the enzymatically digested DNA. Multiple DNA adducts were present in lung, liver and kidney at 1 day after administration. One of the major adducts in lung (20% of the total eluted radioactivity) coeluted with the synthetic marker, N-(deoxyguanosin-8-yl)-1-aminopyrene (C8-dG-AP). This adduct (10% of total eluted radioactivity) and others were still present in the lung at 28 days after administration of 1-NP. One of the adducts in liver and kidney DNA digests also coeluted with C8-dG-AP. Treatment of the adducts with 0.3 M NaOH resulting in earlier eluting peaks containing radioactivity, indicative of an imidazole ring-opening adduct. A portion of the original peak of radioactivity that coeluted with C8-dG-AP and other adducts, however, was not affected by 0.3 M NaOH. Thus, the chromatographic properties and chemical behavior of the adducts formed in vivo suggest that one of the adducts in the lung is C8-dG-AP which is formed by nitroreduction of 1-NP. Other adducts may be formed via ring-oxidation followed in some instances by nitroreduction. These data indicate that DNA adducts of 1-NP metabolites may be formed in the lung (a primary site for inhaled particles), liver and kidney following inhalation of airborne particles containing 1-NP.

Preparing for vocational choice.

Adolescents are often overwhelmed and disillusioned by the monumental and momentous task and risk of making a career choice. Adults in general and counselors in particular can assist them not only in being more realistic about their career expectations, but can be especially helpful by encouraging them to develop personal attributes and skills.

Differential induction of cytochrome P-450 catalyzed activities by polychlorinated biphenyls and benzo [a]pyrene in B6C3F1 mouse liver and lung.

The properties of some constitutive and inducible enzyme activities of liver and lung microsomes were determined in B6C3F1 mice pretreated by either intratracheal (i.t.) administration of benzo[a]pyrene (BaP) or polychlorinated biphenyl (PCBs) mixture (Aroclor 1254), or intraperitoneal (i.p.) administration with Aroclor 1254. After i.p. administration of Aroclor 1254, liver cytochrome P-450 content, aryl hydrocarbon hydroxylase (AHH), benzphetamine N-demethylase and nitroreductase activities were increased 2.8-, 2.0-, 2.2-, and 2.0-fold, respectively. Lung cytochrome P-450 content was also increased (1.9-fold) after i.p. administration of Aroclor 1254; AHH and nitroreductase activities, however, were not affected and benzphetamine N-demethylase activity was decreased. Aroclor 1254 administered i.t. did not affect liver cytochrome P-450 content. However, AHH and benzphetamine N-demethylase activities were decreased 1.4- and 1.2-fold, respectively, and nitroreductase activity was increased 1.6-fold. After i.t. administration of Aroclor 1254, lung cytochrome P-450 content and AHH activity were increased 1.4- and 2.2-fold, respectively. Benzphetamine N-demethylase activity was decreased 2.1-fold and nitroreductase activity was not affected. After i.t. administration of BaP, liver 7-ethoxyresorufin O-deethylase and nitroreductase activities were increased 2.2- and 1.5-fold, respectively, and benzphetamine N-demethylase activity was decreased 1.3-fold. Lung AHH and 7-ethoxyresorufin O-deethylase activities were increased 4.3- and 3.1-fold, respectively, and cytochrome P-450 content, benzphetamine N-demethylase and nitroreductase activities were decreased 1.4-, 1.2- and 1.3-fold, respectively, after BaP administration. These data indicate that different cytochrome P-450 isozymes induced in B6C3F1 mice are responsible for monooxygenase and nitroreductase activities, and that the route of administration of chemicals is important in the expression of cytochrome P-450 catalyzed activities.

Identification of DNA damage as a result of exposure of rats to diesel engine exhaust.

Owing to the concern regarding genotoxic agents which may be present in diesel engine emissions we have studied the effect, with respect to DNA damage, of the exposure of F344 rats to such emissions for approximately 31 months at levels of particulate material of 7.1 mg/m3. Rats were killed and the DNA extracted from the right lung lobe and coded prior to analysis for DNA adducts by the 32P-postlabeling technique. Although a gradation of adduct intensity was found from high levels to none being detectable, distinction could be made between exposed and unexposed groups based upon the intensity of DNA adducts present.