Influence of perinatal nicotine administration on transplacental carcinogenesis in Sprague Dawley rats by N-methylnitrosourea

Abstract

Summary The administration of nicotine during the perinatal stages of life resulted in a significant decrease in tumours occurring after transplacental induction by N-methylnitrosourea (MNU). The overall tumour incidence following p.o. application of MNU to dams was 85% in rats of the F,-generation, the main occurrence being related to the neurogenic system (62% of the animals). Regular injections of nicotine before or after birth resulted in a reduction of malignancies by 17% and 22% (P=0.08 and 0.0015), respectively. The difference in the incidence of neurogenic tumours proved to be highly significant (P<0.002) in rats of either sex, when nicotine was applied over 26 weeks following birth. There was a gender-specific imbalance in rats which received the carcinogen only, in favour of a lower tumour yield in females (P<0.04), which became less apparent when nicotine was given additionally. These findings suggest that nicotine is capable of modulating the expression of chemically induced tumours of the neurogenic system in a favourable way. Antonomov, 1976). The importance of the respective single agents in tobacco smoke in the mechanisms of tumour development is the field of current research. To avoid a multitude of concurrent mechanisms that are active in tobacco smoke, it seems necessary to investigate at first the effects of purified compounds in order to identify their inherent risk precisely.Since nicotine is the main attraction when consuming cigarettes, this constituent was primarily tested for a possible carcinogenic action. The majority of these studies revealed that neither nicotine nor its primary metabolites were carcinogenic (LaVoie et al., 1985;Martin et al., 1979;Schmahl & Osswald, 1968;Toth, 1982), although two studies indicated a weak tumorigenic action (Boyland, 1968; Truhaut et al., 1984). Furthermore, a limited number of studies were concerned with a possible modulation of carcinogenesis by nicotine (Bock, 1980;Gurkalo & Volfson, 1982;Habs & Schmahl, 1976Ito et al., 1984; LaVoie et al., 1985). These authors used well-established chemicallyinduced models for the detection of nicotine-related changes in tumour expression. Since no uniform answer was obtained from these studies, the question remains whether certain types of cancer can be influenced specifically by nicotine (Bock, 1980;Gurkalo & Volfson, 1982; LaVoie et al., 1985) and whether especially sensitive periods of life exist such as the perinatal period, in which even a very low dose of this agent can lead to tumour development. The latter assumption could be relevant, since a remarkable number of women do not change their smoking habits during pregnancy and subsequent lactation period. This is the case, even though the influence of nicotine on the progeny has been established in terms of underweight births in animals as well as man (Becker et al., 1968;Becker & Martin, 1971;Martin et al., 1979 Heidelberg, FRG). Both compounds were dissolved in water at 0.4% and 1 %, respectively; fresh solutions were prepared before each administ...

A systematic review of preclinical studies evaluating the association between nicotine and the initiation and progression of cancer

“…The majority of included studies used mice, eight studies used rats ( 35 , 37 - 43 ), and three studies used hamsters ( 44 - 46 ). Across the 50 of the 61 included studies that reported sample size for the nicotine and control groups, total sample size ranged from six to 858 animals, for a total of 3,987 animals included across all studies that reported sample size.…”

“…Among the 61 included studies, 45 studies were randomized controlled trials (RCTs), and the remaining 16 studies were controlled, parallel group studies. The most common method of administration was oral administration of nicotine in drinking water ( 36 , 42 , 45 , 47 - 66 ), followed by intraperitoneal injections ( 34 , 40 , 41 , 55 , 67 - 83 ), subcutaneous injections or subcutaneous continuous infusions ( 37 - 39 , 43 , 84 - 90 ), and buccal administration ( 46 , 91 , 92 ). Other methods of nicotine administration, used in one study each, included application of a dermal patch ( 70 ), intravenous injections ( 36 ), gavage ( 93 ), and inhalation ( 35 ).…”

“…Across the 61 included studies, 19 studies evaluated digestive cancers ( 44 , 45 , 48 , 51 , 56 , 61 , 64 - 68 , 71 , 72 , 76 , 79 , 80 , 84 , 87 , 93 ), 19 studies evaluated lung cancers ( 36 , 47 , 49 , 50 , 52 , 54 , 55 , 57 , 58 , 62 , 70 , 73 , 77 , 81 , 83 , 86 , 88 - 90 ), six studies evaluated breast cancers ( 34 , 38 , 53 , 60 , 74 , 75 ), six studies evaluated head and neck cancers ( 46 , 69 , 78 , 91 , 92 , 94 ), and two studies evaluated urinary tract cancers ( 42 , 82 ). Nine studies evaluated other cancer types, or evaluated cancers at multiple sites ( 35 , 37 , 39 - 41 , 43 , 59 , 63 , 85 ). Most studies used a xenograft or an allograft tumor model, 14 studies used a carcinogen-induced tumor model ( 37 , 38 , 42 , 45 , 46 , 55 , 57 , 58 , 65 , <...…”

“…Nine studies evaluated other cancer types, or evaluated cancers at multiple sites ( 35 , 37 , 39 - 41 , 43 , 59 , 63 , 85 ). Most studies used a xenograft or an allograft tumor model, 14 studies used a carcinogen-induced tumor model ( 37 , 38 , 42 , 45 , 46 , 55 , 57 , 58 , 65 , 70 , 73 , 84 , 87 , 91 ), and four studies used a genetic tumor model ( 51 , 55 , 59 , 62 ). Four studies used more than one tumor model within the same study: three studies used a xenograft and a carcinogen-induced tumor model ( 58 , 70 , 91 ), and one study used a carcinogen-induced tumor model, a genetic tumor model, and an allograft tumor model ( 55 ).…”

“…Four studies used more than one tumor model within the same study: three studies used a xenograft and a carcinogen-induced tumor model ( 58 , 70 , 91 ), and one study used a carcinogen-induced tumor model, a genetic tumor model, and an allograft tumor model ( 55 ). Thirteen studies evaluated the spontaneous occurrence of tumors after the administration of nicotine ( 35 , 37 - 39 , 41 , 43 , 44 , 46 , 55 , 57 , 63 , 85 , 91 ).…”